ArticleThe Journal of biological chemistry2010
Defining the molecular basis of BubR1 kinetochore interactions and APC/C-CDC20 inhibition.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Linking kinetochore attachment to checkpoint control: the role of Aurora B in BubR1 acetylation.Nucleic acids research · 2026Article
- Alternative use of droxidopa for treating cervical cancer: inhibiting transferase, cell cycle signalling, and transport proteins via multitarget docking, DFT, MD simulations, and binding free energy studies.Medical oncology (Northwood, London, England) · 2025Article
- Evaluating the multitargeted potency of Pixuvri against cell cycle regulation proteins in cervical cancer.Frontiers in oncology · 2025Article
- Unveiling the potency of FDA-approved oxidopamine HBr for cervical cancer regulation and replication proteins.Medical oncology (Northwood, London, England) · 2024Article
- Multitargeted inhibitory effect of Mitoxantrone 2HCl on cervical cancer cell cycle regulatory proteins: a multitargeted docking-based MM\GBSA and MD simulation study.Medical oncology (Northwood, London, England) · 2023Article
- Seeing is believing: our evolving view of kinetochore structure, composition, and assembly.Current opinion in cell biology · 2019Review
- Leader of the SAC: molecular mechanisms of Mps1/TTK regulation in mitosis.Open biology · 2018Review
- Association between polymorphisms in segregation genes BUB1B and TTK and gastric cancer risk.Radiology and oncology · 2016Article
- The mitotic checkpoint complex (MCC): looking back and forth after 15 years.AIMS molecular science · 2016Article
- Bub3-BubR1-dependent sequestration of Cdc20Fizzy at DNA breaks facilitates the correct segregation of broken chromosomes.The Journal of cell biology · 2015Article
- Signalling dynamics in the spindle checkpoint response.Nature reviews. Molecular cell biology · 2014Review
- Bimodal activation of BubR1 by Bub3 sustains mitotic checkpoint signaling.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- A TPR domain-containing N-terminal module of MPS1 is required for its kinetochore localization by Aurora B.The Journal of cell biology · 2013Article
- Use of the protein ontology for multi-faceted analysis of biological processes: a case study of the spindle checkpoint.Frontiers in genetics · 2013Article
- Deformations within moving kinetochores reveal different sites of active and passive force generation.Science (New York, N.Y.) · 2012Article
- Structure of the mitotic checkpoint complex.Nature · 2012Article
- Structural analysis reveals features of the spindle checkpoint kinase Bub1-kinetochore subunit Knl1 interaction.The Journal of cell biology · 2012Article
- Characterization of spindle checkpoint kinase Mps1 reveals domain with functional and structural similarities to tetratricopeptide repeat motifs of Bub1 and BubR1 checkpoint kinases.The Journal of biological chemistry · 2012Article
- The architecture of the BubR1 tetratricopeptide tandem repeat defines a protein motif underlying mitotic checkpoint-kinetochore communication.Bioarchitecture · 2012Article
- Mechanistic insights into aging, cell-cycle progression, and stress response.Frontiers in physiology · 2012Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
BubR1 is essential for the mitotic checkpoint that prevents aneuploidy in cellular progeny by triggering anaphase delay in response to kinetochores incorrectly/not attached to the mitotic spindle. Here, we define the molecular architecture of the functionally significant N-terminal region of human BubR1 and present the 1.8 A crystal structure of its tetratricopeptide repeat (TPR) domain. The structure reveals divergence from the classical TPR fold and is highly similar to the TPR domain of budding yeast Bub1. Shared distinctive features include a disordered loop insertion, a 3(10)-helix, a tight turn involving glycine positive Phi angles, and noncanonical packing of and between the TPR motifs. We also define the molecular determinants of the interaction between BubR1 and kinetochore protein Blinkin. We identify a shallow groove on the concave surface of the BubR1 TPR domain that forms multiple discrete and potentially cooperative interactions with Blinkin. Finally, we present evidence for a direct interaction between BubR1 and Bub1 mediated by regions C-terminal to their TPR domains. This interaction provides a mechanism for Bub1-dependent kinetochore recruitment of BubR1. We thus present novel molecular insights into the structure of BubR1 and its interactions at the kinetochore-microtubule interface. Our studies pave the way for future structure-directed engineering aimed at dissecting the roles of kinetochore-bound and other pools of BubR1 in vivo.
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