BubR1 TPR domain supports the mitotic checkpoint by promoting MCC formation and MCC-APC/C interaction
Abstract via Europe PMC
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.
Evidence snapshot note
This reference is cited by the validated MVA · BUB1B evidence snapshot (data as of 2026-10-17) as BUBR1 TPR / MCC–APC/C functional controls.
- Model in the source
- HeLa endogenous BUBR1 RNAi and RNAi-resistant YFP replacement
- Where in the publication
- Figure 4B; supplementary source-data workbook, Sheet1
- Cited by evidence records
- MVA-CTRL-006
The note describes how the snapshot used the source; it is not a summary of the publication's conclusions.
Identifiers and provenance
- DOI
10.1038/s42003-026-10384-9- PMID
42477419- PMCID
PMC13385977- Metadata from
- Crossref, Europe PMC, OpenAlex, fetched
- License (as declared by the source)
- https://creativecommons.org/licenses/by-nc-nd/4.0
- Open access
- Yes
- Added
- from the MVA evidence snapshot
In the library
- Collections
- MVA Hackathon 2026 — BUB1B
- Tags
- None yet
- Keywords from the source
- BubR1, tetratricopeptide repeat domain, spindle assembly checkpoint, mitotic checkpoint complex, anaphase-promoting complex, Mad2, CDC20, APC2, chromosome segregation, kinetochore attachment, intramolecular interactions