Cited by 172Microtubule and mitosis dynamicsCancer-related Molecular PathwaysUbiquitin and proteasome pathways

BubR1 N Terminus Acts as a Soluble Inhibitor of Cyclin B Degradation by APC/CCdc20 in Interphase

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Malureanu, Liviu A., Jeganathan, Karthik B., Hamada, Masakazu, Wasilewski, Lisa, Davenport, James, van Deursen, Jan M.·2009·Developmental Cell

Abstract

BubR1 is an essential mitotic checkpoint protein with multiple functional domains. It has been implicated in mitotic checkpoint control, as an active kinase at unattached kinetochores, and as a cytosolic inhibitor of APC/C(Cdc20) activity, as well as in mitotic timing and stable chromosome-spindle attachment. Using BubR1-conditional knockout cells and BubR1 domain mutants, we demonstrate that the N-terminal Cdc20 binding domain of BubR1 is essential for all of these functions, whereas its C-terminal Cdc20-binding domain, Bub3-binding domain, and kinase domain are not. We find that the BubR1 N terminus binds to Cdc20 in a KEN box-dependent manner to inhibit APC/C activity in interphase, thereby allowing accumulation of cyclin B in G(2) phase prior to mitosis onset. Together, our results suggest that kinetochore-bound BubR1 is nonessential and that soluble BubR1 functions as a pseudosubstrate inhibitor of APC/C(Cdc20) during interphase to prevent unscheduled degradation of specific APC/C substrates.

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Crossref · 10.1016/j.devcel.2008.11.004

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Authors
Malureanu, L. A., Jeganathan, K. B., Hamada, M., Wasilewski, L., Davenport, J., & van Deursen, J. M.
Affiliations
  • Mayo Clinic (US)
  • St. Jude Children's Research Hospital (US)
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2009-01
Volume
16
Issue
1
Pages
118-131
ISSN
1534-5807 (ISSN-L)
OpenAlex
W2048994246
Cited by
172
References
34
Citations by year
2026: 1 · 2025: 3 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 8 · 2019: 8 · 2018: 3 · 2017: 5 · 2016: 13 · 2015: 13 · 2014: 17 · 2013: 14 · 2012: 17
FWCI
11.13
Type
journal article
Language
en
Open access
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Ellison Medical Foundation
  • National Institutes of Health
  • National Cancer Institute (CA-96985, R01CA096985)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
Keywords
BubR1, CDC20, anaphase-promoting complex, cyclin B degradation, KEN box, spindle assembly checkpoint, interphase, G2 phase, Bub3, kinetochore, mitotic timing
MeSH terms
Animals, Cell Survival, Cells, Cultured, Chromosomes, Fibroblasts, Humans, Interphase, Spindle Apparatus, Recombinant Fusion Proteins, Tumor Suppressor Protein p53, Protein Serine-Threonine Kinases, Mice, Knockout, Cell Cycle Proteins, Cyclin B, Ubiquitin-Protein Ligase Complexes, Mice, Anaphase-Promoting Complex-Cyclosome, Cdc20 Proteins

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