ArticleMolecular cell2013
Catalytic assembly of the mitotic checkpoint inhibitor BubR1-Cdc20 by a Mad2-induced functional switch in Cdc20.
Article in Molecular cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60 citing papers in PubMed, 97 citations in OpenAlex.
- Molecular mechanism of Mad2 conformational conversion promoted by the Mad2-interaction motif of Cdc20.Protein science : a publication of the Protein Society · 2025Article
- Chromothripsis: an emerging crossroad from aberrant mitosis to therapeutic opportunities.Journal of molecular cell biology · 2024Review
- CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Kinetochore-catalyzed MCC formation: A structural perspective.IUBMB life · 2023Article
- Juxtaposition of Bub1 and Cdc20 on phosphorylated Mad1 during catalytic mitotic checkpoint complex assembly.Nature communications · 2022Article
- Research progress of Bub3 gene in malignant tumors.Cell biology international · 2022Review
- The Role of the APC/C and Its Coactivators Cdh1 and Cdc20 in Cancer Development and Therapy.Frontiers in genetics · 2022Review
- PIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression.Scientific reports · 2021Article
- Spindle assembly checkpoint activation and silencing at kinetochores.Seminars in cell & developmental biology · 2021Review
- A tripartite mechanism catalyzes Mad2-Cdc20 assembly at unattached kinetochores.Science (New York, N.Y.) · 2021Article
- The Role of CHK1 Varies with the Status of Oestrogen-receptor and Progesterone-receptor in the Targeted Therapy for Breast Cancer.International journal of biological sciences · 2020Article
- Deficiency of PTEN leads to aberrant chromosome segregation through downregulation of MAD2.Molecular medicine reports · 2019Article
- TRIP13 and APC15 drive mitotic exit by turnover of interphase- and unattached kinetochore-produced MCC.Nature communications · 2018Article
- Perturbing mitosis for anti-cancer therapy: is cell death the only answer?EMBO reports · 2018Review
- Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C).Open biology · 2017Review
- BubR1 Promotes Bub3-Dependent APC/C Inhibition during Spindle Assembly Checkpoint Signaling.Current biology : CB · 2017Article
- The AAA+ ATPase TRIP13 remodels HORMA domains through N-terminal engagement and unfolding.The EMBO journal · 2017Article
- A Dynamical Model for Activating and Silencing the Mitotic Checkpoint.Scientific reports · 2017Article
- "Wait anaphase" signals are not confined to the mitotic spindle.Molecular biology of the cell · 2017Article
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6 authors at 3 institutions in 1 country.
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Abstract
The mitotic checkpoint acts to maintain chromosome content by generation of a diffusible anaphase inhibitor. Unattached kinetochores catalyze a conformational shift in Mad2, converting an inactive open form into a closed form that can capture Cdc20, the mitotic activator of the APC/C ubiquitin ligase. Mad2 binding is now shown to promote a functional switch in Cdc20, exposing a previously inaccessible site for binding to BubR1's conserved Mad3 homology domain. BubR1, but not Mad2, binding to APC/C(Cdc20) is demonstrated to inhibit ubiquitination of cyclin B. Closed Mad2 is further shown to catalytically amplify production of BubR1-Cdc20 without necessarily being part of the complex. Thus, the mitotic checkpoint is produced by a cascade of two catalytic steps: an initial step acting at unattached kinetochores to produce a diffusible Mad2-Cdc20 intermediate and a diffusible step in which that intermediate amplifies production of BubR1-Cdc20, the inhibitor of cyclin B ubiquitination, by APC/C(Cdc20).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.