| CENP-A reduction induces a p53-dependent cellular senescence response to protect cells from executing defective mitoses. | |
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MedLine Citation:
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PMID: 20160010 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cellular senescence is an irreversible growth arrest and is presumed to be a natural barrier to tumor development. Like telomere shortening, certain defects in chromosome integrity can trigger senescence; however, the roles of centromere proteins in regulating commitment to the senescent state remains to be established. We examined chromatin structure in senescent human primary fibroblasts and found that CENP-A protein levels are diminished in senescent cells. Senescence-associated reduction of CENP-A is caused by transcriptional and posttranslational control. Surprisingly, forced reduction of CENP-A by short-hairpin RNA was found to cause premature senescence in human primary fibroblasts. This premature senescence is dependent on a tumor suppressor, p53, but not on p16(INK4a)-Rb; the depletion of CENP-A in p53-deficient cells results in aberrant mitosis with chromosome missegregation. We propose that p53-dependent senescence that arises from CENP-A reduction acts as a "self-defense mechanism" to prevent centromere-defective cells from undergoing mitotic proliferation that potentially leads to massive generation of aneuploid cells. |
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Authors:
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Kayoko Maehara; Kohta Takahashi; Shigeaki Saitoh |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-16 |
Journal Detail:
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Title: Molecular and cellular biology Volume: 30 ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-04-08 Completed Date: 2010-04-22 Revised Date: 2010-11-02 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 2090-104 Citation Subset: IM |
Affiliation:
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Department of Maternal-Fetal Biology, National Center for Child Health and Development, 2-10-1, Okura, Setagaya-ku, Tokyo 157-8535, Japan. kmaehara@nch.go.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Autoantigens
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metabolism* Cell Aging* Cell Line Cell Proliferation Cells, Cultured Chromosomal Proteins, Non-Histone / deficiency, metabolism* Cyclin-Dependent Kinase Inhibitor p16 / metabolism Cytoprotection* Fibroblasts / cytology*, metabolism* Gene Expression Regulation Heterochromatin / metabolism Humans Mitosis* Phenotype Protein Biosynthesis Protein Processing, Post-Translational RNA, Small Interfering / metabolism Receptors, Retinoic Acid / metabolism Retinoblastoma Protein / metabolism Transcription, Genetic Tumor Suppressor Protein p53 / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Autoantigens; 0/Chromosomal Proteins, Non-Histone; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Heterochromatin; 0/RARRES3 protein, human; 0/RNA, Small Interfering; 0/Receptors, Retinoic Acid; 0/Retinoblastoma Protein; 0/Tumor Suppressor Protein p53; 0/centromere protein A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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