| The mitotic checkpoint: a signaling pathway that allows a single unattached kinetochore to inhibit mitotic exit. | |
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MedLine Citation:
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PMID: 14593737 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The mitotic checkpoint is a failsafe mechanism for the cell to ensure accurate chromosome segregation during mitosis. Mutations in genes encoding essential checkpoint proteins lead to chromosome instability and promote carcinogenesis. The BUB and MAD genes are essential components of the mitotic checkpoint pathway. BUB and MAD inhibit the ubiquitin ligase activity of the Anaphase Promoting Complex/Cyclosome (APC/C) during mitosis to ensure cells with unaligned chromosomes do not prematurely enter anaphase. Two models explain how the APC/C is inhibited by the checkpoint. The Sequestration Model postulates that Mad2 and BubR1 bind and sequester Cdc20, an APC/C activator, away from APC/C so substrates whose destruction drives mitotic exit are no longer ubiquitinated. In this model, the unattached kinetochore is postulated to catalytically convert Mad2 to a form that binds Cdc20. In the Direct Inhibition Model, the Mitotic Checkpoint Complex (MCC) consisting of BubR1, Bub3, Mad2 and Cdc20 binds and inhibits the APC/C independently of the kinetochore. However, the "wait anaphase" signal generated by unattached kinetochores sensitizes the APC/C to prolonged inhibition by the MCC. A single unattached kinetochore is proposed to amplify the "wait anaphase" signal through a kinase cascade involving checkpoint kinases such as hBubR1, hBub1 and Mps1. |
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Authors:
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Gordon K Chan; Tim J Yen |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review |
Journal Detail:
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Title: Progress in cell cycle research Volume: 5 ISSN: 1087-2957 ISO Abbreviation: Prog Cell Cycle Res Publication Date: 2003 |
Date Detail:
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Created Date: 2003-11-03 Completed Date: 2003-12-11 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9609058 Medline TA: Prog Cell Cycle Res Country: United States |
Other Details:
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Languages: eng Pagination: 431-9 Citation Subset: IM |
Affiliation:
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Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada T6G 1Z2. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anaphase
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genetics* Animals Calcium-Binding Proteins / genetics Carrier Proteins* Cell Cycle Proteins / genetics* Fungal Proteins / genetics Genes, cdc / physiology* Humans Kinetochores / physiology* Mitosis / genetics* Nuclear Proteins Protein Kinases / genetics Protein-Serine-Threonine Kinases Signal Transduction / genetics* Ubiquitin-Protein Ligase Complexes / genetics |
| Grant Support | |
ID/Acronym/Agency:
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CA06927/CA/NCI NIH HHS; GM44762/GM/NIGMS NIH HHS; P01 CA75138/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Calcium-Binding Proteins; 0/Carrier Proteins; 0/Cell Cycle Proteins; 0/Fungal Proteins; 0/Nuclear Proteins; EC 2.7.-/Protein Kinases; EC 2.7.11.1/Bub1 spindle checkpoint protein; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 6.3.2.19/Ubiquitin-Protein Ligase Complexes; EC 6.3.2.19/anaphase-promoting complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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