| BTG2 antagonizes Pin1 in response to mitogens and telomere disruption during replicative senescence. | |
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MedLine Citation:
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PMID: 20569234 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Cellular senescence limits the replicative capacity of normal cells and acts as an intrinsic barrier that protects against the development of cancer. Telomere shortening-induced replicative senescence is dependent on the ATM-p53-p21 pathway but additional genes likely contribute to senescence. Here, we show that the p53-responsive gene BTG2 plays an essential role in replicative senescence. Similar to p53 and p21 depletion, BTG2 depletion in human fibroblasts leads to an extension of cellular lifespan, and ectopic BTG2 induces senescence independently of p53. The anti-proliferative function of BTG2 during senescence involves its stabilization in response to telomere dysfunction followed by serum-dependent binding and relocalization of the cell cycle regulator prolyl isomerase Pin1. Pin1 inhibition leads to senescence in late-passage cells, and ectopic Pin1 expression rescues cells from BTG2-induced senescence. The neutralization of Pin1 by BTG2 provides a critical mechanism to maintain senescent arrest in the presence of mitogenic signals in normal primary fibroblasts. |
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Authors:
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Keith Wheaton; Jennifer Muir; Weili Ma; Samuel Benchimol |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-08-04 |
Journal Detail:
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Title: Aging cell Volume: 9 ISSN: 1474-9726 ISO Abbreviation: Aging Cell Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101130839 Medline TA: Aging Cell Country: England |
Other Details:
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Languages: eng Pagination: 747-60 Citation Subset: IM |
Copyright Information:
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© 2010 The Authors Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland. |
Affiliation:
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Department of Biology, York University, Toronto, Ontario, Canada. kwheaton@yorku.ca |
Export Citation:
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Descriptor/Qualifier:
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| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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