{"ok":true,"items":[{"id":"seed-bubr1-tpr-2026","sourceId":"10.1038/s42003-026-10384-9","venue":"Communications Biology","abstractSource":"europepmc","keywords":["BubR1","tetratricopeptide repeat domain","spindle assembly checkpoint","mitotic checkpoint complex","anaphase-promoting complex","Mad2","CDC20","APC2","chromosome segregation","kinetochore attachment","intramolecular interactions"],"sources":["crossref","europepmc","openalex"],"year":2026,"source":"crossref","title":"BubR1 TPR domain supports the mitotic checkpoint by promoting MCC formation and MCC-APC/C interaction","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":true,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Communications Biology","year":2026,"title":"BubR1 TPR domain supports the mitotic checkpoint by promoting MCC formation and MCC-APC/C interaction","type":"research-article","authors":["Mingzhe Zhang","Tingting Lei","Ying Wang","Mingyan Li","Yutong Wang","Jing Fang","Gang Zhang"]},"publishedAt":"2026-07-20","fetchedAt":"2026-10-24T17:05:00.351Z","abstract":"BubR1 is a key component of the mitotic checkpoint, a surveillance mechanism which ensures accurate chromosome segregation by facilitating the assembly of the mitotic checkpoint complex (MCC) and promoting its binding to the anaphase-promoting complex/cyclosome (APC/C). Although BubR1's role in the mitotic checkpoint has been extensively investigated, the function of its N-terminal tetratricopeptide repeat (TPR) domain remains poorly understood. In this study, we first establish the essential role of the BubR1 TPR domain in the mitotic checkpoint. Guided by the resolved cryo-EM structure of the MCC-APC/C complex, we identify and characterize several interactions between the BubR1 TPR domain and Mad2, Cdc20 APC/C and Apc2. Furthermore, we discover an intramolecular interaction between the TPR domain and downstream residues of BubR1, which appears to organize a structure resembling a \"lasso\" that incorporates four Cdc20 APC/C -binding elements, thereby enhancing engagement with Cdc20 in the APC/C. Functional and biochemical analyses demonstrate that these interactions collectively promote MCC assembly and MCC-APC/C binding, enabling rapid SAC activation in response to microtubule-kinetochore attachment defects.","pmid":"42477419","url":"https://www.nature.com/articles/s42003-026-10384-9","tags":[],"readingStatus":"reviewed","license":"https://creativecommons.org/licenses/by-nc-nd/4.0","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1038/s42003-026-10384-9","collectionIds":["mva-bub1b"],"publisher":"Springer Science and Business Media LLC","caseIds":["mvabub1b"],"pmcid":"PMC13385977","snapshot":{"sourceId":"bubr1-tpr-2026","dataAsOf":"2026-10-17","location":"Figure 4B; supplementary source-data workbook, Sheet1","model":"HeLa endogenous BUBR1 RNAi and RNAi-resistant YFP replacement","label":"BUBR1 TPR / MCC–APC/C functional controls","recordIds":["MVA-CTRL-006"]},"authors":["Mingzhe Zhang","Tingting Lei","Ying Wang","Mingyan Li","Yutong Wang","Jing Fang","Gang Zhang"],"doi":"10.1038/s42003-026-10384-9","graphNodeId":"pub:seed-bubr1-tpr-2026"},{"id":"seed-torban-2025","sourceId":"10.1038/s41598-025-26775-7","venue":"Scientific Reports","abstractSource":"europepmc","keywords":["Therapy","Aminoglycosides","Readthrough Drugs","Autosomal-dominant Polycystic Kidney Disease","Premature Termination Codon"],"sources":["crossref","europepmc","openalex"],"year":2025,"source":"crossref","title":"Translational readthrough therapy for ADPKD induces polycystin1 expression and partially rescues functional deficits in PKD1 mutant cells","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":true,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Scientific Reports","year":2025,"title":"Translational readthrough therapy for ADPKD induces polycystin1 expression and partially rescues functional deficits in PKD1 mutant cells","type":"research-article","authors":["Elena Torban","Lucie Canaff","Sima Babayeva","Nadezda Kachurina","Chen-Fang Chung","Albert C. M. Ong","Ahsan Alam","Paul R. Goodyer"]},"publishedAt":"2025-11-22","fetchedAt":"2026-10-24T17:05:01.423Z","abstract":"Autosomal-Dominant Polycystic Kidney Disease, ADPKD, is the most common genetic kidney disease affecting 1:1000 people worldwide. It is caused by mutations in the PKD1 (~ 80%) or PKD2 gene (~ 15%). Although the germline mutation is inherited in dominant fashion, disabling the second allele is required for emergence of clonal cysts. Presently, no cure exists for ADPKD. In approximately 30% of patients, the heritable ADPKD mutation involves a single nucleotide substitution that converts the normal mRNA triplet encoding an amino acid into a Premature Termination Codon (PTC). The translation machinery poses at the PTC and detaches from the mutant mRNA; the unstable transcript and protein are degraded. Certain aminoglycosides bind to the mammalian ribosome and relax translational fidelity, permitting continued translation and production of a full-length protein. In this study, we tested the ability of aminoglycosides to induce readthrough of the PTC codons in the human PKD1 gene and ascertained the effect of these drugs on pathologic features of PKD1 mutant cells. We report that aminoglycosides induce 8-25% expression of full-length Polycystin1 (PKD1 gene product) and significantly improve aberrant cell adhesion and cell signaling. Based on our observations, we propose that aminoglycoside readthrough drugs show potential as therapeutic agents for ADPKD.","pmid":"41274954","url":"https://www.nature.com/articles/s41598-025-26775-7","tags":[],"readingStatus":"reviewed","license":"https://creativecommons.org/licenses/by-nc-nd/4.0","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1038/s41598-025-26775-7","collectionIds":["mva-bub1b"],"publisher":"Springer Science and Business Media LLC","caseIds":["mvabub1b"],"pmcid":"PMC12663426","snapshot":{"sourceId":"torban-2025","dataAsOf":"2026-10-17","location":"Figures 1H-I, 4, 5 and 6; published 2025-11-22","model":"Human HEK293 PKD1 reporters and WT9-12 cells; other-gene evidence","label":"Torban et al. — PKD1 readthrough and partial cellular rescue","recordIds":["MVA-RT-TRANSFER-009"]},"authors":["Elena Torban","Lucie Canaff","Sima Babayeva","Nadezda Kachurina","Chen-Fang Chung","Albert C. M. Ong","Ahsan Alam","Paul R. Goodyer"],"doi":"10.1038/s41598-025-26775-7","graphNodeId":"pub:seed-torban-2025"},{"id":"seed-toledano-2024","sourceId":"10.1038/s41588-024-01878-5","venue":"Nature Genetics","abstractSource":"crossref","keywords":["nonsense suppression","stop codon readthrough","premature stop codon","nonsense mutation","small molecule drugs","drug efficacy prediction","sequence context","tumor suppressor inactivation","genetic disorders","personalized treatment"],"sources":["crossref","europepmc","openalex"],"year":2024,"source":"crossref","title":"Genome-scale quantification and prediction of pathogenic stop codon readthrough by small molecules","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":true,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Nature Genetics","year":2024,"title":"Genome-scale quantification and prediction of pathogenic stop codon readthrough by small molecules","type":"research-article","authors":["Ignasi Toledano","Fran Supek","Ben Lehner"]},"publishedAt":"2024-09","fetchedAt":"2026-10-24T17:04:59.476Z","abstract":"Abstract Premature termination codons (PTCs) cause ~10–20% of inherited diseases and are a major mechanism of tumor suppressor gene inactivation in cancer. A general strategy to alleviate the effects of PTCs would be to promote translational readthrough. Nonsense suppression by small molecules has proven effective in diverse disease models, but translation into the clinic is hampered by ineffective readthrough of many PTCs. Here we directly tackle the challenge of defining drug efficacy by quantifying the readthrough of ~5,800 human pathogenic stop codons by eight drugs. We find that different drugs promote the readthrough of complementary subsets of PTCs defined by local sequence context. This allows us to build interpretable models that accurately predict drug-induced readthrough genome-wide, and we validate these models by quantifying endogenous stop codon readthrough. Accurate readthrough quantification and prediction will empower clinical trial design and the development of personalized nonsense suppression therapies.","pmid":"39174735","url":"https://www.nature.com/articles/s41588-024-01878-5","tags":[],"readingStatus":"reviewed","license":"https://creativecommons.org/licenses/by/4.0","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1038/s41588-024-01878-5","collectionIds":["mva-bub1b"],"publisher":"Springer Science and Business Media LLC","caseIds":["mvabub1b"],"pmcid":"PMC11387191","snapshot":{"sourceId":"toledano-2024","dataAsOf":"2026-10-17","location":"Supplementary Table 3; Extended Data Figure 4","model":"Human HEK293T landing-pad reporters; not endogenous BUB1B","label":"Toledano et al. — genome-scale PTC readthrough","recordIds":["MVA-RT-002"]},"authors":["Ignasi Toledano","Fran Supek","Ben Lehner"],"doi":"10.1038/s41588-024-01878-5","graphNodeId":"pub:seed-toledano-2024"},{"id":"seed-her2-sarcoma-2024","sourceId":"10.1038/s43018-024-00749-6","venue":"Nature Cancer","abstractSource":null,"keywords":["HER2","chimeric antigen receptor T cells","autologous CAR T-cell therapy","advanced sarcoma","lymphocyte depletion","fludarabine","cyclophosphamide","cytokine release syndrome","anticancer activity","tumor immune microenvironment"],"sources":["crossref","europepmc","openalex"],"year":2024,"source":"crossref","title":"Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":false,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Nature Cancer","year":2024,"title":"Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial","type":"research-article","authors":["Meenakshi Hegde","Shoba Navai","Christopher DeRenzo","Sujith K. Joseph","Khaled Sanber","Mengfen Wu","Ahmed Z. Gad","Katherine A. Janeway","Matthew Campbell","Dolores Mullikin","Zeid Nawas","Catherine Robertson","Pretty R. Mathew","Huimin Zhang","Birju Mehta","Raksha R. Bhat","Angela Major","Ankita Shree","Claudia Gerken","Mamta Kalra","Rikhia Chakraborty","Sachin G. Thakkar","Olga Dakhova","Vita S. Salsman","Bambi Grilley","Natalia Lapteva","Adrian Gee","Gianpietro Dotti","Riyue Bao","Ahmed Hamed Salem","Tao Wang","Malcolm K. Brenner","Helen E. Heslop","Winfried S. Wels","M. John Hicks","Stephen Gottschalk","Nabil Ahmed"]},"publishedAt":"2024-04-24","fetchedAt":"2026-10-24T17:05:02.547Z","abstract":"","pmid":"38658775","url":"https://www.nature.com/articles/s43018-024-00749-6","tags":[],"readingStatus":"reviewed","license":"https://www.springernature.com/gp/researchers/text-and-data-mining","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1038/s43018-024-00749-6","collectionIds":["mva-bub1b"],"publisher":"Springer Science and Business Media LLC","caseIds":["mvabub1b"],"pmcid":"PMC11588040","snapshot":{"sourceId":"her2-sarcoma-2024","dataAsOf":"2026-10-17","location":"Abstract; Table 1 and response results / Figure 4 located through indexed primary-article text.","model":"People with progressive HER2-positive sarcoma, including rhabdomyosarcoma.","label":"Autologous HER2-specific CAR T cells after lymphodepletion for advanced sarcoma: a phase 1 trial","recordIds":["MVA-IMMUNE-011"]},"authors":["Meenakshi Hegde","Shoba Navai","Christopher DeRenzo","Sujith K. Joseph","Khaled Sanber","Mengfen Wu","Ahmed Z. Gad","Katherine A. Janeway","Matthew Campbell","Dolores Mullikin","Zeid Nawas","Catherine Robertson","Pretty R. Mathew","Huimin Zhang","Birju Mehta","Raksha R. Bhat","Angela Major","Ankita Shree","Claudia Gerken","Mamta Kalra","Rikhia Chakraborty","Sachin G. Thakkar","Olga Dakhova","Vita S. Salsman","Bambi Grilley","Natalia Lapteva","Adrian Gee","Gianpietro Dotti","Riyue Bao","Ahmed Hamed Salem","Tao Wang","Malcolm K. Brenner","Helen E. Heslop","Winfried S. Wels","M. John Hicks","Stephen Gottschalk","Nabil Ahmed"],"doi":"10.1038/s43018-024-00749-6","graphNodeId":"pub:seed-her2-sarcoma-2024"},{"id":"seed-amor-2024","sourceId":"10.1038/s43587-023-00560-5","venue":"Nature Aging","abstractSource":"crossref","keywords":["cellular senescence","urokinase-type plasminogen activator receptor","uPAR","exercise capacity","glucose tolerance","high-fat diet","single-dose therapy","aging","senolytics"],"sources":["crossref","europepmc","openalex"],"year":2024,"source":"crossref","title":"Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":true,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Nature Aging","year":2024,"title":"Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction","type":"research-article","authors":["Corina Amor","Inés Fernández-Maestre","Saria Chowdhury","Yu-Jui Ho","Sandeep Nadella","Courtenay Graham","Sebastian E. Carrasco","Emmanuella Nnuji-John","Judith Feucht","Clemens Hinterleitner","Valentin J. A. Barthet","Jacob A. Boyer","Riccardo Mezzadra","Matthew G. Wereski","David A. Tuveson","Ross L. Levine","Lee W. Jones","Michel Sadelain","Scott W. Lowe"]},"publishedAt":"2024-01-24","fetchedAt":"2026-10-24T17:05:02.330Z","abstract":"Abstract Senescent cells, which accumulate in organisms over time, contribute to age-related tissue decline. Genetic ablation of senescent cells can ameliorate various age-related pathologies, including metabolic dysfunction and decreased physical fitness. While small-molecule drugs that eliminate senescent cells (‘senolytics’) partially replicate these phenotypes, they require continuous administration. We have developed a senolytic therapy based on chimeric antigen receptor (CAR) T cells targeting the senescence-associated protein urokinase plasminogen activator receptor (uPAR), and we previously showed these can safely eliminate senescent cells in young animals. We now show that uPAR-positive senescent cells accumulate during aging and that they can be safely targeted with senolytic CAR T cells. Treatment with anti-uPAR CAR T cells improves exercise capacity in physiological aging, and it ameliorates metabolic dysfunction (for example, improving glucose tolerance) in aged mice and in mice on a high-fat diet. Importantly, a single administration of these senolytic CAR T cells is sufficient to achieve long-term therapeutic and preventive effects.","pmid":"38267706","url":"https://www.nature.com/articles/s43587-023-00560-5","tags":[],"readingStatus":"reviewed","license":"https://creativecommons.org/licenses/by/4.0","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1038/s43587-023-00560-5","collectionIds":["mva-bub1b"],"publisher":"Springer Science and Business Media LLC","caseIds":["mvabub1b"],"pmcid":"PMC10950785","snapshot":{"sourceId":"amor-2024","dataAsOf":"2026-10-17","location":"Figures 3-5 (clearance, safety assessments and metabolic endpoints); Figures 6-7 (persistence/prevention and high-fat diet).","model":"Naturally aged C57BL/6 mice and high-fat-diet mice.","label":"Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction","recordIds":["MVA-IMMUNE-011"]},"authors":["Corina Amor","Inés Fernández-Maestre","Saria Chowdhury","Yu-Jui Ho","Sandeep Nadella","Courtenay Graham","Sebastian E. Carrasco","Emmanuella Nnuji-John","Judith Feucht","Clemens Hinterleitner","Valentin J. A. Barthet","Jacob A. Boyer","Riccardo Mezzadra","Matthew G. Wereski","David A. Tuveson","Ross L. Levine","Lee W. Jones","Michel Sadelain","Scott W. Lowe"],"doi":"10.1038/s43587-023-00560-5","graphNodeId":"pub:seed-amor-2024"},{"id":"seed-gdap1-2023","sourceId":"10.3390/ph16071034","venue":"Pharmaceuticals","abstractSource":"crossref","keywords":["Cmt Disease","Nonsense Mutation","Premature Termination Codon (Ptc)","Nonsense-mediated Decay (Nmd)","Gdap1","Readthrough Molecules"],"sources":["crossref","europepmc","openalex"],"year":2023,"source":"crossref","title":"Amlexanox: Readthrough Induction and Nonsense-Mediated mRNA Decay Inhibition in a Charcot–Marie–Tooth Model of hiPSCs-Derived Neuronal Cells Harboring a Nonsense Mutation in GDAP1 Gene","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":true,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Pharmaceuticals","year":2023,"title":"Amlexanox: Readthrough Induction and Nonsense-Mediated mRNA Decay Inhibition in a Charcot–Marie–Tooth Model of hiPSCs-Derived Neuronal Cells Harboring a Nonsense Mutation in GDAP1 Gene","type":"research-article","authors":["Nesrine Benslimane","Federica Miressi","Camille Loret","Laurence Richard","Angélique Nizou","Ioanna Pyromali","Pierre-Antoine Faye","Frédéric Favreau","Fabrice Lejeune","Anne-Sophie Lia"]},"publishedAt":"2023-07-21","fetchedAt":"2026-10-24T17:05:01.667Z","abstract":"Nonsense mutations are involved in multiple peripheral neuropathies. These mutations induce the presence of a premature termination codon (PTC) at the mRNA level. As a result, a dysfunctional or truncated protein is synthesized, or even absent linked to nonsense-mediated mRNA degradation (NMD) system activation. Readthrough molecules or NMD inhibitors could be innovative therapies in these hereditary neuropathies, particularly molecules harboring the dual activity as amlexanox. Charcot–Marie–Tooth (CMT) is the most common inherited pathology of the peripheral nervous system, affecting 1 in 2500 people worldwide. Nonsense mutations in the GDAP1 gene have been associated with a severe form of CMT, prompting us to investigate the effect of readthrough and NMD inhibitor molecules. Although not clearly defined, GDAP1 could be involved in mitochondrial functions, such as mitophagy. We focused on the homozygous c.581C>G (p.Ser194*) mutation inducing CMT2H using patient human induced pluripotent stem cell (hiPSC)-derived neuronal cells. Treatment during 20 h with 100 µM of amlexanox on this cell model stabilized GDAP1 mRNAs carrying UGA-PTC and induced a restoration of the mitochondrial morphology. These results highlight the potential of readthrough molecules associated to NMD inhibitors for the treatment of genetic alterations in CMT, opening the way for future investigations and a potential therapy.","pmid":"37513945","url":"https://doi.org/10.3390/ph16071034","tags":[],"readingStatus":"reviewed","license":"https://creativecommons.org/licenses/by/4.0/","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.3390/ph16071034","collectionIds":["mva-bub1b"],"publisher":"MDPI AG","caseIds":["mvabub1b"],"pmcid":"PMC10385573","snapshot":{"sourceId":"gdap1-2023","dataAsOf":"2026-10-17","location":"Figures 2-4","model":"Human iPSC-derived neuronal progenitors with GDAP1 p.Ser194* (UGA)","label":"Amlexanox in GDAP1 neuronal progenitors","recordIds":["MVA-AMLEXANOX-010"]},"authors":["Nesrine Benslimane","Federica Miressi","Camille Loret","Laurence Richard","Angélique Nizou","Ioanna Pyromali","Pierre-Antoine Faye","Frédéric Favreau","Fabrice Lejeune","Anne-Sophie Lia"],"doi":"10.3390/ph16071034","graphNodeId":"pub:seed-gdap1-2023"},{"id":"seed-nivolumab-ipilimumab-2022","sourceId":"10.1158/1078-0432.ccr-22-2164","venue":"Clinical Cancer Research","abstractSource":"openalex","keywords":["nivolumab","ipilimumab","immune checkpoint inhibitors","combination immunotherapy","pediatric solid tumors","relapsed/refractory cancer","children and young adults","Ewing sarcoma","rhabdomyosarcoma","osteosarcoma","dose-limiting toxicity","immune-related adverse events"],"sources":["crossref","europepmc","openalex"],"year":2022,"source":"crossref","title":"A Phase I/II Trial of Nivolumab plus Ipilimumab in Children and Young Adults with Relapsed/Refractory Solid Tumors: A Children's Oncology Group Study ADVL1412","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":false,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Clinical Cancer Research","year":2022,"title":"A Phase I/II Trial of Nivolumab plus Ipilimumab in Children and Young Adults with Relapsed/Refractory Solid Tumors: A Children's Oncology Group Study ADVL1412","type":"research-article","authors":["Kara L. Davis","Elizabeth Fox","Emasenyie Isikwei","Joel M. Reid","Xiaowei Liu","Charles G. Minard","Stephan Voss","Stacey L. Berg","Brenda J. Weigel","Crystal L. Mackall"]},"publishedAt":"2022-12-01","fetchedAt":"2026-10-24T17:05:02.966Z","abstract":"PURPOSE: In many cancers, nivolumab in combination with ipilimumab improves response rates compared with either agent alone, but the combination has not been evaluated in childhood cancer. We conducted a phase I/II trial of nivolumab plus ipilimumab in children and young adults with recurrent/refractory solid tumors. PATIENTS AND METHODS: ADVL1412, Part C assessed safety of nivolumab plus ipilimumab at two dose levels (DL): DL1 1 mg/kg of each drug and DL2 3 mg/kg nivolumab plus 1 mg/kg ipilimumab. Part D evaluated response at the recommended phase II dose (RP2D) in Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma. Part E tested DL3 (1 mg/kg nivolumab plus 3 mg/kg ipilimumab) in Ewing sarcoma and rhabdomyosarcoma. Tumor response was measured using RECIST v1.1. Pharmacokinetics and PD-L1 expression on archival tissues were assessed. RESULTS: Fifty-five eligible patients enrolled. Based on safety, tolerability, and similar drug exposure to the same doses administered in adults, DL2 was defined as the pediatric RP2D. Among 41 patients treated at the RP2D, 2 patients experienced dose-limiting toxicities during cycle 1, and 4 patients experienced toxicities beyond that period. Two patients had clinically significant sustained partial responses (1 rhabdomyosarcoma, 1 Ewing sarcoma) and 4 had stable disease. Among 8 patients treated at DL3, 3 dose-limiting toxicities (DLT) occurred, all immune-related adverse events; no objective responses were observed. CONCLUSIONS: The RP2D of nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg) is well tolerated in children and young adults with solid tumors and shows some clinical activity. Increased dose of ipilimumab (3 mg/kg) plus nivolumab (1 mg/kg) was associated with increased toxicity without clinical benefit.","pmid":"36190525","url":"https://doi.org/10.1158/1078-0432.CCR-22-2164","tags":[],"readingStatus":"reviewed","license":null,"corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1158/1078-0432.ccr-22-2164","collectionIds":["mva-bub1b"],"publisher":"American Association for Cancer Research (AACR)","caseIds":["mvabub1b"],"pmcid":"PMC10597535","snapshot":{"sourceId":"nivolumab-ipilimumab-2022","dataAsOf":"2026-10-17","location":"Abstract reproduced by the investigators at Children's Oncology Group; Figure 3A located in indexed primary text.","model":"Children and young adults with recurrent/refractory solid tumors.","label":"A Phase I/II Trial of Nivolumab Plus Ipilimumab in Children and Young Adults with Relapsed/Refractory Solid Tumors: ADVL1412","recordIds":["MVA-IMMUNE-011"]},"authors":["Kara L. Davis","Elizabeth Fox","Emasenyie Isikwei","Joel M. Reid","Xiaowei Liu","Charles G. Minard","Stephan Voss","Stacey L. Berg","Brenda J. Weigel","Crystal L. Mackall"],"doi":"10.1158/1078-0432.ccr-22-2164","graphNodeId":"pub:seed-nivolumab-ipilimumab-2022"},{"id":"seed-steurer-2022","sourceId":"10.1007/s12033-022-00467-3","venue":"Molecular Biotechnology","abstractSource":"crossref","keywords":["Heat shock response","Neurodegenerative disease","Luciferase assay","Hsf1"],"sources":["crossref","europepmc","openalex"],"year":2022,"source":"crossref","title":"Quantitative Comparison of HSF1 Activators","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":true,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Molecular Biotechnology","year":2022,"title":"Quantitative Comparison of HSF1 Activators","type":"research-article","authors":["Christoph Steurer","Sarah Kerschbaum","Christina Wegrostek","Stefan Gabriel","Ali Hallaj","Viktoria Ortner","Thomas Czerny","Elisabeth Riegel"]},"publishedAt":"2022-08","fetchedAt":"2026-10-24T17:05:00.919Z","abstract":"Abstract The heat shock response (HSR) pathway is a highly conserved rescue mechanism, which protects the cells from harmful insults disturbing the cellular protein homeostasis via expression of chaperones. Furthermore, it was demonstrated to play crucial roles in various diseases like neurodegeneration and cancer. For neurodegenerative diseases, an overexpression of chaperones is a potential therapeutic approach to clear the cells from non-functional protein aggregates. Therefore, activators of the HSR pathway and its master regulator HSF1 are under close observation. There are numerous HSR activators published in the literature using different model systems, experimental designs, and readout assays. The aim of this work was to provide a quantitative comparison of a broad range of published activators using a newly developed HSF responsive dual-luciferase cell line. Contrary to natural target genes, which are regulated by multiple input pathways, the artificial reporter exclusively reacts to HSF activity. In addition, the results were compared to endogenous heat shock protein expression. As a result, great differences in the intensity of pathway activation were observed. In addition, a parallel viability assessment revealed high variability in the specificity of the drugs. Furthermore, the differences seen compared to published data indicate that some activators exhibit tissue-specific differences leading to interesting assumptions about the regulation of HSF1.","pmid":"35218516","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9259536/","tags":[],"readingStatus":"reviewed","license":"https://creativecommons.org/licenses/by/4.0","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1007/s12033-022-00467-3","collectionIds":["mva-bub1b"],"publisher":"Springer Science and Business Media LLC","caseIds":["mvabub1b"],"pmcid":"PMC9259536","snapshot":{"sourceId":"steurer-2022","dataAsOf":"2026-10-17","location":"Table 1 and Figure 4: negative arimoclomol response in this system","model":"Human HSF-responsive reporter and endogenous target systems","label":"Steurer et al. — HSF1 reporter evaluation","recordIds":["MVA-ARI-007"]},"authors":["Christoph Steurer","Sarah Kerschbaum","Christina Wegrostek","Stefan Gabriel","Ali Hallaj","Viktoria Ortner","Thomas Czerny","Elisabeth Riegel"],"doi":"10.1007/s12033-022-00467-3","graphNodeId":"pub:seed-steurer-2022"},{"id":"seed-omachi-2022","sourceId":"10.1016/j.isci.2022.103891","venue":"iScience","abstractSource":"europepmc","keywords":["Molecular biology","Biochemistry","Molecular Medicine"],"sources":["crossref","europepmc","openalex"],"year":2022,"source":"crossref","title":"NanoLuc reporters identify COL4A5 nonsense mutations susceptible to drug-induced stop codon readthrough","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":true,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"iScience","year":2022,"title":"NanoLuc reporters identify COL4A5 nonsense mutations susceptible to drug-induced stop codon readthrough","type":"research-article","authors":["Kohei Omachi","Hirofumi Kai","Michel Roberge","Jeffrey H. Miner"]},"publishedAt":"2022-03","fetchedAt":"2026-10-24T17:04:59.633Z","abstract":"Alport syndrome, a disease of kidney, ear, and eye, is caused by pathogenic variants in the COL4A3 , COL4A4 , or COL4A5 genes encoding collagen α3α4α5(IV) of basement membranes. Collagen IV chains that are truncated due to nonsense variants/premature termination codons (PTCs) cannot assemble into heterotrimers or incorporate into basement membranes. To investigate the feasibility of PTC readthrough therapy for Alport syndrome, we utilized two NanoLuc reporters in transfected cells: full-length for monitoring translation, and a split version for assessing readthrough product function. Full-length assays of 49 COL4A5 nonsense variants identified eleven as susceptible to PTC readthrough using various readthrough drugs. In split-NanoLuc assays, the predicted missense α5(IV) readthrough products of five nonsense mutations could heterotrimerize with α3(IV) and α4(IV). Readthrough was also observed in kidney cells from an engineered Col4a5 PTC mouse model. These results suggest that readthrough therapy is a feasible approach for a fraction of patients with Alport syndrome.","pmid":"35243249","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8866893/","tags":[],"readingStatus":"reviewed","license":"https://www.elsevier.com/tdm/userlicense/1.0/","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1016/j.isci.2022.103891","collectionIds":["mva-bub1b"],"publisher":"Elsevier BV","caseIds":["mvabub1b"],"pmcid":"PMC8866893","snapshot":{"sourceId":"omachi-2022","dataAsOf":"2026-10-17","location":"Figure 6: gentamicin plus mefloquine","model":"HEK293 COL4A5 cDNA reporters; different gene and context","label":"Omachi et al. — COL4A5 readthrough reporters","recordIds":["MVA-RT-002"]},"authors":["Kohei Omachi","Hirofumi Kai","Michel Roberge","Jeffrey H. Miner"],"doi":"10.1016/j.isci.2022.103891","graphNodeId":"pub:seed-omachi-2022"},{"id":"seed-zhao-2021","sourceId":"10.1016/j.omtn.2021.12.003","venue":"Molecular Therapy Nucleic Acids","abstractSource":"europepmc","keywords":["Mitoxantrone","artesunate","albendazole","Gabexate Mesilate","Montelukast Sodium","Topotecan Hydrochloride","Tra2b","Ptbp2","Hnrnpl","Trazodone Hydrochloride"],"sources":["crossref","europepmc","openalex"],"year":2022,"source":"crossref","title":"Molecular profiling of individual FDA-approved clinical drugs identifies modulators of nonsense-mediated mRNA decay","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":true,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Molecular Therapy Nucleic Acids","year":2022,"title":"Molecular profiling of individual FDA-approved clinical drugs identifies modulators of nonsense-mediated mRNA decay","type":"research-article","authors":["Jingrong Zhao","Zhelin Li","Ruchira Puri","Kelvin Liu","Israel Nunez","Liang Chen","Sika Zheng"]},"publishedAt":"2022-03","fetchedAt":"2026-10-24T17:04:59.101Z","abstract":"Nonsense-mediated mRNA decay (NMD) degrades transcripts with premature stop codons. Given the prevalence of nonsense single nucleotide polymorphisms (SNPs) in the general population, it is urgent to catalog the effects of clinically approved drugs on NMD activity: any interference could alter the expression of nonsense SNPs, inadvertently inducing adverse effects. This risk is higher for patients with disease-causing nonsense mutations or an illness linked to dysregulated nonsense transcripts. On the other hand, hundreds of disorders are affected by cellular NMD efficiency and may benefit from NMD-modulatory drugs. Here, we profiled individual FDA-approved drugs for their impact on cellular NMD efficiency using a sensitive method that directly probes multiple endogenous NMD targets for a robust readout of NMD modulation. We found most FDA-approved drugs cause unremarkable effects on NMD, while many elicit clear transcriptional responses. Besides several potential mild NMD modulators, the anticancer drug homoharringtonine (HHT or omacetaxine mepesuccinate) consistently upregulates various endogenous NMD substrates in a dose-dependent manner in multiple cell types. We further showed translation inhibition mediates HHT's NMD effect. In summary, many FDA drugs induce transcriptional changes, and a few impact global NMD, and direct measurement of endogenous NMD substrate expression is robust to monitor cellular NMD.","pmid":"35024243","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC8718828/","tags":[],"readingStatus":"reviewed","license":"https://www.elsevier.com/tdm/userlicense/1.0/","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1016/j.omtn.2021.12.003","collectionIds":["mva-bub1b"],"publisher":"Elsevier BV","caseIds":["mvabub1b"],"pmcid":"PMC8718828","snapshot":{"sourceId":"zhao-2021","dataAsOf":"2026-10-17","location":"Tables S1/S2/S4; Figures 2–5 and 7","model":"Mouse Neuro-2a; three AS-NMD isoform reporters","label":"Zhao et al. — molecular profiling of NMD modulators","recordIds":["MVA-NMD-003","MVA-AMLEXANOX-010"]},"authors":["Jingrong Zhao","Zhelin Li","Ruchira Puri","Kelvin Liu","Israel Nunez","Liang Chen","Sika Zheng"],"doi":"10.1016/j.omtn.2021.12.003","graphNodeId":"pub:seed-zhao-2021"},{"id":"seed-nefl-2022","sourceId":"10.3389/fcell.2021.820105","venue":"Frontiers in Cell and Developmental Biology","abstractSource":"crossref","keywords":["Axon","Induced Pluripotent Stem Cells","Charcot-marie-tooth (Cmt) Disease","Neurofilament Light (Nfl)","Motor Neurodegeneration","Motor Neuron (Mn)"],"sources":["crossref","europepmc","openalex"],"year":2022,"source":"crossref","title":"Neurofilament Light Regulates Axon Caliber, Synaptic Activity, and Organelle Trafficking in Cultured Human Motor Neurons","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":true,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Frontiers in Cell and Developmental Biology","year":2022,"title":"Neurofilament Light Regulates Axon Caliber, Synaptic Activity, and Organelle Trafficking in Cultured Human Motor Neurons","type":"research-article","authors":["Markus T. Sainio","Tiina Rasila","Svetlana M. Molchanova","Julius Järvilehto","Rubén Torregrosa-Muñumer","Sandra Harjuhaahto","Jana Pennonen","Nadine Huber","Sanna-Kaisa Herukka","Annakaisa Haapasalo","Henrik Zetterberg","Tomi Taira","Johanna Palmio","Emil Ylikallio","Henna Tyynismaa"]},"publishedAt":"2022-02-14","fetchedAt":"2026-10-24T17:05:02.062Z","abstract":"Neurofilament light (NFL) is one of the proteins forming multimeric neuron-specific intermediate filaments, neurofilaments, which fill the axonal cytoplasm, establish caliber growth, and provide structural support. Dominant missense mutations and recessive nonsense mutations in the neurofilament light gene ( NEFL ) are among the causes of Charcot–Marie–Tooth (CMT) neuropathy, which affects the peripheral nerves with the longest axons. We previously demonstrated that a neuropathy-causing homozygous nonsense mutation in NEFL led to the absence of NFL in patient-specific neurons. To understand the disease-causing mechanisms, we investigate here the functional effects of NFL loss in human motor neurons differentiated from induced pluripotent stem cells (iPSC). We used genome editing to generate NEFL knockouts and compared them to patient-specific nonsense mutants and isogenic controls. iPSC lacking NFL differentiated efficiently into motor neurons with normal axon growth and regrowth after mechanical axotomy and contained neurofilaments. Electrophysiological analysis revealed that motor neurons without NFL fired spontaneous and evoked action potentials with similar characteristics as controls. However, we found that, in the absence of NFL, human motor neurons 1) had reduced axonal caliber, 2) the amplitude of miniature excitatory postsynaptic currents (mEPSC) was decreased, 3) neurofilament heavy (NFH) levels were reduced and no compensatory increases in other filament subunits were observed, and 4) the movement of mitochondria and to a lesser extent lysosomes was increased. Our findings elaborate the functional roles of NFL in human motor neurons. NFL is not only a structural protein forming neurofilaments and filling the axonal cytoplasm, but our study supports the role of NFL in the regulation of synaptic transmission and organelle trafficking. To rescue the NFL deficiency in the patient-specific nonsense mutant motor neurons, we used three drugs, amlexanox, ataluren (PTC-124), and gentamicin to induce translational read-through or inhibit nonsense-mediated decay. However, the drugs failed to increase the amount of NFL protein to detectable levels and were toxic to iPSC-derived motor neurons.","pmid":"35237613","url":"https://doi.org/10.3389/fcell.2021.820105","tags":[],"readingStatus":"reviewed","license":"https://creativecommons.org/licenses/by/4.0/","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.3389/fcell.2021.820105","collectionIds":["mva-bub1b"],"publisher":"Frontiers Media SA","caseIds":["mvabub1b"],"pmcid":"PMC8883324","snapshot":{"sourceId":"nefl-2022","dataAsOf":"2026-10-17","location":"Figure 6; Treatments","model":"Human iPSC-derived NEFL nonsense motor neurons","label":"NEFL motor-neuron negative rescue","recordIds":["MVA-AMLEXANOX-010"]},"authors":["Markus T. Sainio","Tiina Rasila","Svetlana M. Molchanova","Julius Järvilehto","Rubén Torregrosa-Muñumer","Sandra Harjuhaahto","Jana Pennonen","Nadine Huber","Sanna-Kaisa Herukka","Annakaisa Haapasalo","Henrik Zetterberg","Tomi Taira","Johanna Palmio","Emil Ylikallio","Henna Tyynismaa"],"doi":"10.3389/fcell.2021.820105","graphNodeId":"pub:seed-nefl-2022"},{"id":"seed-nivolumab-2020","sourceId":"10.1016/s1470-2045(20)30023-1","venue":"The Lancet Oncology","abstractSource":null,"keywords":["PD-1 inhibitors","childhood cancer","lymphoma","rhabdomyosarcoma","Ewing sarcoma","osteosarcoma","neuroblastoma","Hodgkin's disease","non-Hodgkin lymphoma","melanoma","immune checkpoint inhibitors","safety and tolerability"],"sources":["crossref","europepmc","openalex"],"year":2020,"source":"crossref","title":"Nivolumab in children and young adults with relapsed or refractory solid tumours or lymphoma (ADVL1412): a multicentre, open-label, single-arm, phase 1–2 trial","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":false,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"The Lancet Oncology","year":2020,"title":"Nivolumab in children and young adults with relapsed or refractory solid tumours or lymphoma (ADVL1412): a multicentre, open-label, single-arm, phase 1–2 trial","type":"research-article","authors":["Kara L Davis","Elizabeth Fox","Melinda S Merchant","Joel M Reid","Rachel A Kudgus","Xiaowei Liu","Charles G Minard","Stephan Voss","Stacey L Berg","Brenda J Weigel","Crystal L Mackall"]},"publishedAt":"2020-04","fetchedAt":"2026-10-24T17:05:02.790Z","abstract":"","pmid":"32192573","url":"https://doi.org/10.1016/S1470-2045(20)30023-1","tags":[],"readingStatus":"reviewed","license":"https://www.elsevier.com/tdm/userlicense/1.0/","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1016/s1470-2045(20)30023-1","collectionIds":["mva-bub1b"],"publisher":"Elsevier BV","caseIds":["mvabub1b"],"pmcid":"PMC7255545","snapshot":{"sourceId":"nivolumab-2020","dataAsOf":"2026-10-17","location":"Abstract, findings and interpretation; no figure-level extraction.","model":"Pediatric and young-adult relapsed/refractory malignancies; phase 1-2.","label":"Nivolumab in children and young adults with relapsed or refractory solid tumours or lymphoma (ADVL1412)","recordIds":["MVA-IMMUNE-011"]},"authors":["Kara L Davis","Elizabeth Fox","Melinda S Merchant","Joel M Reid","Rachel A Kudgus","Xiaowei Liu","Charles G Minard","Stephan Voss","Stacey L Berg","Brenda J Weigel","Crystal L Mackall"],"doi":"10.1016/s1470-2045(20)30023-1","graphNodeId":"pub:seed-nivolumab-2020"},{"id":"seed-sieben-2020","sourceId":"10.1172/jci126863","venue":"Journal of Clinical Investigation","abstractSource":"openalex","keywords":["Aging","Cancer","Cellular senescence","Oncology","Genetic diseases"],"sources":["crossref","europepmc","openalex"],"year":2019,"source":"crossref","title":"BubR1 allelic effects drive phenotypic heterogeneity in mosaic-variegated aneuploidy progeria syndrome","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":false,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Journal of Clinical Investigation","year":2019,"title":"BubR1 allelic effects drive phenotypic heterogeneity in mosaic-variegated aneuploidy progeria syndrome","type":"research-article","authors":["Cynthia J. Sieben","Karthik B. Jeganathan","Grace G. Nelson","Ines Sturmlechner","Cheng Zhang","Willemijn H. van Deursen","Bjorn Bakker","Floris Foijer","Hu Li","Darren J. Baker","Jan M. van Deursen"]},"publishedAt":"2019-11-18","fetchedAt":"2026-10-24T17:05:00.205Z","abstract":"Mosaic-variegated aneuploidy (MVA) syndrome is a rare childhood disorder characterized by biallelic BUBR1, CEP57, or TRIP13 aberrations; increased chromosome missegregation; and a broad spectrum of clinical features, including various cancers, congenital defects, and progeroid pathologies. To investigate the mechanisms underlying this disorder and its phenotypic heterogeneity, we mimicked the BUBR1L1012P mutation in mice (BubR1L1002P) and combined it with 2 other MVA variants, BUBR1X753 and BUBR1H, generating a truncated protein and low amounts of wild-type protein, respectively. Whereas BubR1X753/L1002P and BubR1H/X753 mice died prematurely, BubR1H/L1002P mice were viable and exhibited many MVA features, including cancer predisposition and various progeroid phenotypes, such as short lifespan, dwarfism, lipodystrophy, sarcopenia, and low cardiac stress tolerance. Strikingly, although these mice had a reduction in total BUBR1 and spectrum of MVA phenotypes similar to that of BubR1H/H mice, several progeroid pathologies were attenuated in severity, which in skeletal muscle coincided with reduced senescence-associated secretory phenotype complexity. Additionally, mice carrying monoallelic BubR1 mutations were prone to select MVA-related pathologies later in life, with predisposition to sarcopenia correlating with mTORC1 hyperactivity. Together, these data demonstrate that BUBR1 allelic effects beyond protein level and aneuploidy contribute to disease heterogeneity in both MVA patients and heterozygous carriers of MVA mutations.","pmid":"31738183","url":"https://www.jci.org/articles/view/126863","tags":[],"readingStatus":"reviewed","license":"other-oa","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1172/jci126863","collectionIds":["mva-bub1b"],"publisher":"American Society for Clinical Investigation","caseIds":["mvabub1b"],"pmcid":"PMC6934189","snapshot":{"sourceId":"sieben-2020","dataAsOf":"2026-10-17","location":"Abstract and Figures 1-3; related variant, not N1002K","model":"Mouse BubR1 L1002P ortholog model of human L1012P with hypomorphic or truncating alleles","label":"Sieben et al. — allelic effects in MVA progeria syndrome","recordIds":["MVA-N1002K-GATE-002"]},"authors":["Cynthia J. Sieben","Karthik B. Jeganathan","Grace G. Nelson","Ines Sturmlechner","Cheng Zhang","Willemijn H. van Deursen","Bjorn Bakker","Floris Foijer","Hu Li","Darren J. Baker","Jan M. van Deursen"],"doi":"10.1172/jci126863","graphNodeId":"pub:seed-sieben-2020"},{"id":"seed-deane-2016","sourceId":"10.1007/s12192-016-0708-2","venue":"Cell Stress and Chaperones","abstractSource":"openalex","keywords":["Heat shock","Celastrol","Arimoclomol","Hspa1a (Hsp70-1)","Hspa6 (Hsp70b’)","Human Sh-sy5y Neuronal Cells"],"sources":["crossref","europepmc","openalex"],"year":2016,"source":"crossref","title":"Induction of heat shock proteins in differentiated human neuronal cells following co-application of celastrol and arimoclomol","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":false,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Cell Stress and Chaperones","year":2016,"title":"Induction of heat shock proteins in differentiated human neuronal cells following co-application of celastrol and arimoclomol","type":"research-article","authors":["Catherine A.S. Deane","Ian R. Brown"]},"publishedAt":"2016-09","fetchedAt":"2026-10-24T17:05:00.500Z","abstract":"Few effective therapies exist for the treatment of neurodegenerative diseases that have been characterized as protein misfolding disorders. Upregulation of heat shock proteins (Hsps) mitigates against the accumulation of misfolded, aggregation-prone proteins and synaptic dysfunction, which is recognized as an early event in neurodegenerative diseases. Enhanced induction of a set of Hsps in differentiated human SH-SY5Y neuronal cells was observed following co-application of celastrol and arimoclomol, compared to their individual application. The dosages employed did not affect cell viability or neuronal process morphology. The induced Hsps included the little studied HSPA6 (Hsp70B'), a potentially neuroprotective protein that is present in the human genome but not in rat and mouse and hence is missing in current animal models of neurodegenerative disease. Enhanced induction of HSPA1A (Hsp70-1), DNAJB1 (Hsp40), HO-1 (Hsp32), and HSPB1 (Hsp27) was also observed. Celastrol activates heat shock transcription factor 1 (HSF1), the master regulator of Hsp gene transcription, and also exhibits potent anti-inflammatory and anti-oxidant activities. Arimoclomol is a co-activator that prolongs the binding of activated HSF1 to heat shock elements (HSEs) in the promoter regions of inducible Hsp genes. Elevated Hsp levels peaked at 10 to 12 h for HSPA6, HSPA1A, DNAJB1, and HO-1 and at 24 h for HSPB1. Co-application of celastrol and arimoclomol induced higher Hsp levels compared to heat shock paired with arimoclomol. The co-application strategy of celastrol and arimoclomol targets multiple neurodegenerative disease-associated pathologies including protein misfolding and protein aggregation, inflammatory and oxidative stress, and synaptic dysfunction.","pmid":"27273088","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC5003800/","tags":[],"readingStatus":"reviewed","license":"https://www.elsevier.com/tdm/userlicense/1.0/","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1007/s12192-016-0708-2","collectionIds":["mva-bub1b"],"publisher":"Elsevier BV","caseIds":["mvabub1b"],"pmcid":"PMC5003800","snapshot":{"sourceId":"deane-2016","dataAsOf":"2026-10-17","location":"Figures 2–5; not a BUBR1 study","model":"Differentiated human SH-SY5Y cells; arimoclomol plus celastrol","label":"Deane and Brown — conditional heat-shock co-induction","recordIds":["MVA-ARI-007"]},"authors":["Catherine A.S. Deane","Ian R. Brown"],"doi":"10.1007/s12192-016-0708-2","graphNodeId":"pub:seed-deane-2016"},{"id":"seed-gillespie-2015","sourceId":"10.1080/19491034.2015.1128610","venue":"Nucleus","abstractSource":"openalex","keywords":["Quiescence","Rapamycin","Rna-seq","Primary Fibroblast","Stat5a/b"],"sources":["crossref","europepmc","openalex"],"year":2015,"source":"crossref","title":"Rapamycin reduces fibroblast proliferation without causing quiescence and induces STAT5A/B-mediated cytokine production","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":false,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Nucleus","year":2015,"title":"Rapamycin reduces fibroblast proliferation without causing quiescence and induces STAT5A/B-mediated cytokine production","type":"research-article","authors":["Zoe E Gillespie","Kimberly MacKay","Michelle Sander","Brett Trost","Wojciech Dawicki","Aruna Wickramarathna","John Gordon","Mark Eramian","Ian R Kill","Joanna M Bridger","Anthony Kusalik","Jennifer A Mitchell","Christopher H Eskiw"]},"publishedAt":"2015-11-02","fetchedAt":"2026-10-24T17:05:01.105Z","abstract":"Rapamycin is a well-known inhibitor of the Target of Rapamycin (TOR) signaling cascade; however, the impact of this drug on global genome function and organization in normal primary cells is poorly understood. To explore this impact, we treated primary human foreskin fibroblasts with rapamycin and observed a decrease in cell proliferation without causing cell death. Upon rapamycin treatment chromosomes 18 and 10 were repositioned to a location similar to that of fibroblasts induced into quiescence by serum reduction. Although similar changes in positioning occurred, comparative transcriptome analyses demonstrated significant divergence in gene expression patterns between rapamycin-treated and quiescence-induced fibroblasts. Rapamycin treatment induced the upregulation of cytokine genes, including those from the Interleukin (IL)-6 signaling network, such as IL-8 and the Leukemia Inhibitory Factor (LIF), while quiescent fibroblasts demonstrated up-regulation of genes involved in the complement and coagulation cascade. In addition, genes significantly up-regulated by rapamycin treatment demonstrated increased promoter occupancy of the transcription factor Signal Transducer and Activator of Transcription 5A/B (STAT5A/B). In summary, we demonstrated that the treatment of fibroblasts with rapamycin decreased proliferation, caused chromosome territory repositioning and induced STAT5A/B-mediated changes in gene expression enriched for cytokines.","pmid":"26652669","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC4915505/","tags":[],"readingStatus":"reviewed","license":null,"corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1080/19491034.2015.1128610","collectionIds":["mva-bub1b"],"publisher":"Informa UK Limited","caseIds":["mvabub1b"],"pmcid":"PMC4915505","snapshot":{"sourceId":"gillespie-2015","dataAsOf":"2026-10-17","location":"GSE65145 processed tracks; Figures 1 and 3; Figure S2; Cell culture and RNA-seq methods","model":"2DD normal human foreskin fibroblasts; two biological replicates per condition","label":"Gillespie et al. — rapamycin and normal human fibroblast transcription","recordIds":["MVA-RAP-GSE65145-001"]},"authors":["Zoe E Gillespie","Kimberly MacKay","Michelle Sander","Brett Trost","Wojciech Dawicki","Aruna Wickramarathna","John Gordon","Mark Eramian","Ian R Kill","Joanna M Bridger","Anthony Kusalik","Jennifer A Mitchell","Christopher H Eskiw"],"doi":"10.1080/19491034.2015.1128610","graphNodeId":"pub:seed-gillespie-2015"},{"id":"seed-xu-2013","sourceId":"10.1242/bio.20134051","venue":"Biology Open","abstractSource":"crossref","keywords":["Chromosome Congression","Bubr1","Aurora B","B56-pp2a"],"sources":["crossref","europepmc","openalex"],"year":2013,"source":"crossref","title":"BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":true,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Biology Open","year":2013,"title":"BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression","type":"research-article","authors":["Peng Xu","Elizabeth A. Raetz","Mayumi Kitagawa","David M. Virshup","Sang Hyun Lee"]},"publishedAt":"2013-05-15","fetchedAt":"2026-10-24T17:05:00.038Z","abstract":"Summary BUBR1 is a mitotic phosphoprotein essential for the maintenance of chromosome stability by promoting chromosome congression and proper kinetochore–microtubule (K-fiber) attachment, but the underlying mechanism(s) has remained elusive. Here we identify BUBR1 as a binding partner of the B56 family of Protein Phosphatase 2A regulatory subunits. The interaction between BUBR1 and the B56 family is required for chromosome congression, since point mutations in BUBR1 that block B56 binding abolish chromosome congression. The BUBR1:B56-PP2A complex opposes Aurora B kinase activity, since loss of the complex can be reverted by inhibiting Aurora B. Importantly, we show that the failure of BUBR1 to recruit B56-PP2A also contributes to the chromosome congression defects found in cells derived from patients with the Mosaic Variegated Aneuploidy (MVA) syndrome. Together, we propose that B56-PP2A is a key mediator of BUBR1's role in chromosome congression and functions by antagonizing Aurora B activity at the kinetochore for establishing stable kinetochore–microtubule attachment at the metaphase plate.","pmid":"23789096","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC3654266/","tags":[],"readingStatus":"reviewed","license":"http://creativecommons.org/licenses/by-nc-sa/3.0","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1242/bio.20134051","collectionIds":["mva-bub1b"],"publisher":"The Company of Biologists","caseIds":["mvabub1b"],"pmcid":"PMC3654266","snapshot":{"sourceId":"xu-2013","dataAsOf":"2026-10-17","location":"Figures 2 and 4; equally expressed B56-binding mutants are functional counterexamples","model":"HeLa BUBR1 depletion/reconstitution and BUB1B-mutated MVA fibroblast rescue","label":"Xu et al. — BUBR1 recruits PP2A-B56 for chromosome congression","recordIds":["MVA-N1002K-GATE-002"]},"authors":["Peng Xu","Elizabeth A. Raetz","Mayumi Kitagawa","David M. Virshup","Sang Hyun Lee"],"doi":"10.1242/bio.20134051","graphNodeId":"pub:seed-xu-2013"},{"id":"seed-amlexanox-2012","sourceId":"10.1186/1750-1172-7-58","venue":"Orphanet Journal of Rare Diseases","abstractSource":"europepmc","keywords":["amlexanox","nonsense mutation","nonsense-mediated mRNA decay","genetic disorders","drug repurposing","patient-derived cell lines"],"sources":["crossref","europepmc","openalex"],"year":2012,"source":"crossref","title":"Rescue of nonsense mutations by amlexanox in human cells","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":true,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Orphanet Journal of Rare Diseases","year":2012,"title":"Rescue of nonsense mutations by amlexanox in human cells","type":"research-article","authors":["Sara Gonzalez-Hilarion","Terence Beghyn","Jieshuang Jia","Nadège Debreuck","Gonzague Berte","Kamel Mamchaoui","Vincent Mouly","Dieter C Gruenert","Benoit Déprez","Fabrice Lejeune"]},"publishedAt":"2012-12","fetchedAt":"2026-10-24T17:05:01.576Z","abstract":"Background Nonsense mutations are at the origin of many cancers and inherited genetic diseases. The consequence of nonsense mutations is often the absence of mutant gene expression due to the activation of an mRNA surveillance mechanism called nonsense-mediated mRNA decay (NMD). Strategies to rescue the expression of nonsense-containing mRNAs have been developed such as NMD inhibition or nonsense mutation readthrough. Methods Using a dedicated screening system, we sought molecules capable to block NMD. Additionally, 3 cell lines derived from patient cells and harboring a nonsense mutation were used to study the effect of the selected molecule on the level of nonsense-containing mRNAs and the synthesis of proteins from these mutant mRNAs. Results We demonstrate here that amlexanox, a drug used for decades, not only induces an increase in nonsense-containing mRNAs amount in treated cells, but also leads to the synthesis of the full-length protein in an efficient manner. We also demonstrated that these full length proteins are functional. Conclusions As a result of this dual activity, amlexanox may be useful as a therapeutic approach for diseases caused by nonsense mutations.","pmid":"22938201","url":"https://doi.org/10.1186/1750-1172-7-58","tags":[],"readingStatus":"reviewed","license":"cc by","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1186/1750-1172-7-58","collectionIds":["mva-bub1b"],"publisher":"Springer Science and Business Media LLC","caseIds":["mvabub1b"],"pmcid":"PMC3562214","snapshot":{"sourceId":"amlexanox-2012","dataAsOf":"2026-10-17","location":"Figure 6","model":"Human 6CFSMEo- CFTR nonsense cells","label":"Amlexanox rescue in human cells","recordIds":["MVA-AMLEXANOX-010"]},"authors":["Sara Gonzalez-Hilarion","Terence Beghyn","Jieshuang Jia","Nadège Debreuck","Gonzague Berte","Kamel Mamchaoui","Vincent Mouly","Dieter C Gruenert","Benoit Déprez","Fabrice Lejeune"],"doi":"10.1186/1750-1172-7-58","graphNodeId":"pub:seed-amlexanox-2012"},{"id":"seed-baker-2011","sourceId":"10.1038/nature10600","venue":"Nature","abstractSource":null,"keywords":["cellular senescence","senolytics","senolytic therapy","p16INK4a","senescent cell clearance","aging","age-related diseases","healthspan extension","adipose tissue","skeletal muscle","eye","tissue dysfunction"],"sources":["crossref","europepmc","openalex"],"year":2011,"source":"crossref","title":"Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":false,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Nature","year":2011,"title":"Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders","type":"research-article","authors":["Darren J. Baker","Tobias Wijshake","Tamar Tchkonia","Nathan K. LeBrasseur","Bennett G. Childs","Bart van de Sluis","James L. Kirkland","Jan M. van Deursen"]},"publishedAt":"2011-11","fetchedAt":"2026-10-24T17:05:02.136Z","abstract":"","pmid":"22048312","url":"https://www.nature.com/articles/nature10600","tags":[],"readingStatus":"reviewed","license":"http://www.springer.com/tdm","corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1038/nature10600","collectionIds":["mva-bub1b"],"publisher":"Springer Science and Business Media LLC","caseIds":["mvabub1b"],"pmcid":"PMC3468323","snapshot":{"sourceId":"baker-2011","dataAsOf":"2026-10-17","location":"Abstract; Figures 2-4 public captions.","model":"BubR1 H/H hypomorphic progeroid mice carrying INK-ATTAC.","label":"Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders","recordIds":["MVA-IMMUNE-011"]},"authors":["Darren J. Baker","Tobias Wijshake","Tamar Tchkonia","Nathan K. LeBrasseur","Bennett G. Childs","Bart van de Sluis","James L. Kirkland","Jan M. van Deursen"],"doi":"10.1038/nature10600","graphNodeId":"pub:seed-baker-2011"},{"id":"seed-suijkerbuijk-2010","sourceId":"10.1158/0008-5472.can-09-4319","venue":"Cancer Research","abstractSource":"openalex","keywords":["BubR1","spindle assembly checkpoint","biallelic variants","missense mutations","truncating mutations","chromosome segregation errors","chromosomal instability","protein turnover","microtubule attachment","cancer predisposition syndromes"],"sources":["crossref","europepmc","openalex"],"year":2010,"source":"crossref","title":"Molecular Causes for BUBR1 Dysfunction in the Human Cancer Predisposition Syndrome Mosaic Variegated Aneuploidy","type":"research-article","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":false,"updatedAt":"2026-10-24T17:30:17.875Z","original":{"venue":"Cancer Research","year":2010,"title":"Molecular Causes for BUBR1 Dysfunction in the Human Cancer Predisposition Syndrome Mosaic Variegated Aneuploidy","type":"research-article","authors":["Saskia J.E. Suijkerbuijk","Maria H.J. van Osch","Frank L. Bos","Sandra Hanks","Nazneen Rahman","Geert J.P.L. Kops"]},"publishedAt":"2010-06-15","fetchedAt":"2026-10-24T17:04:59.783Z","abstract":"Genetic mutations in the mitotic regulatory kinase BUBR1 are associated with the cancer-susceptible disorder mosaic variegated aneuploidy (MVA). In patients with biallelic mutations, a missense mutation pairs with a truncating mutation. Here, we show that cell lines derived from MVA patients with biallelic mutations have an impaired mitotic checkpoint, chromosome alignment defects, and low overall BUBR1 abundance. Ectopic expression of BUBR1 restored mitotic checkpoint activity, proving that BUBR1 dysfunction causes chromosome segregation errors in the patients. Combined analysis of patient cells and functional protein replacement shows that all MVA mutations fall in two distinct classes: those that impose specific defects in checkpoint activity or microtubule attachment and those that lower BUBR1 protein abundance. Low protein abundance is the direct result of the absence of transcripts from truncating mutants combined with high protein turnover of missense mutants. In this group of missense mutants, the amino acid change consistently occurs in or near the BUBR1 kinase domain. Our findings provide a molecular explanation for chromosomal instability in patients with biallelic genetic mutations in BUBR1.","pmid":"20516114","url":"https://doi.org/10.1158/0008-5472.CAN-09-4319","tags":[],"readingStatus":"reviewed","license":null,"corrections":[],"createdBy":"seed","canonicalKey":"doi:10.1158/0008-5472.can-09-4319","collectionIds":["mva-bub1b"],"publisher":"American Association for Cancer Research (AACR)","caseIds":["mvabub1b"],"pmcid":"PMC2887387","snapshot":{"sourceId":"suijkerbuijk-2010","dataAsOf":"2026-10-17","location":"Figures 4D and 5; comparator variants, not N1002K","model":"U2OS/HeLa BUBR1 depletion and replacement","label":"Suijkerbuijk et al. — molecular causes of BUBR1 dysfunction","recordIds":["MVA-N1002K-GATE-002","MVA-L737-NMD-FIRST-001"]},"authors":["Saskia J.E. Suijkerbuijk","Maria H.J. van Osch","Frank L. Bos","Sandra Hanks","Nazneen Rahman","Geert J.P.L. Kops"],"doi":"10.1158/0008-5472.can-09-4319","graphNodeId":"pub:seed-suijkerbuijk-2010"},{"id":"seed-amlexanox-label","sourceId":"amlexanox-label","venue":"www.accessdata.fda.gov","abstractSource":null,"keywords":[],"sources":["snapshot"],"year":null,"source":"snapshot","title":"FDA historical Aphthasol label","type":"document","createdAt":"2026-10-24T17:30:17.875Z","isOpenAccess":null,"updatedAt":"2026-10-24T17:30:17.875Z","original":null,"publishedAt":null,"fetchedAt":"2026-10-24T17:05:02.063Z","abstract":"","pmid":null,"url":"https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/20511s002lbl.pdf","tags":[],"readingStatus":"reviewed","license":null,"corrections":[],"createdBy":"seed","canonicalKey":"url:https://www.accessdata.fda.gov/drugsatfda_docs/label/2002/20511s002lbl.pdf","collectionIds":["mva-bub1b"],"publisher":"","caseIds":["mvabub1b"],"pmcid":null,"snapshot":{"sourceId":"amlexanox-label","dataAsOf":"2026-10-17","location":"Pharmacokinetics and Metabolism, page 1","model":"Historical FDA Aphthasol 5% oral-paste label","label":"FDA historical Aphthasol label","recordIds":["MVA-AMLEXANOX-010"]},"authors":[],"doi":null,"graphNodeId":"pub:seed-amlexanox-label"}],"total":21,"page":1,"pages":2,"pageSize":20,"sort":"newest","filters":{"q":"","collection":null,"type":null,"year":null,"source":null,"status":null,"tag":null,"caseId":null}}