| Metabolic stabilization of p27 in senescent fibroblasts correlates with reduced expression of the F-box protein Skp2. | |
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MedLine Citation:
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PMID: 11738146 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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When mortal human cells reach their finite lifespan, they enter an irreversible G1 growth arrest status referred to as senescence. Growth suppression of senescent cells can be explained by the accumulation of several growth-suppressive proteins, acting on mitogenic signal transduction and cell cycle regulation, respectively. We show here that the cdk inhibitor p27(KIP1), which is involved in several forms of G1 checkpoint control, accumulates in senescent cells. Whereas, the rate of p27 synthesis is reduced, accumulation of p27 is accompanied by an increase of the metabolic stability in senescent cells. p27 is a substrate for ubiquitin-mediated proteolysis, and its stabilization in senescent cells correlates with a deregulation of the p27-specific E3 ubiquitin ligase referred to as the SCF complex. Whereas, the Skp1 component of the SCF complex is overexpressed in senescent fibroblasts, the abundance of the F-box protein Skp2 is strongly reduced. In contrast to our findings with p27, the synthesis of the cell cycle regulators p21 and cyclin D1 is increased in senescent cells; however, both proteins are also highly unstable in these cells. |
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Authors:
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M Wagner; B Hampel; E Hütter; G Pfister; W Krek; W Zwerschke; P Jansen-Dürr |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Experimental gerontology Volume: 37 ISSN: 0531-5565 ISO Abbreviation: Exp. Gerontol. Publication Date: 2001 Dec |
Date Detail:
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Created Date: 2001-12-12 Completed Date: 2002-02-25 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0047061 Medline TA: Exp Gerontol Country: England |
Other Details:
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Languages: eng Pagination: 41-55 Citation Subset: IM |
Affiliation:
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Institut f. Biomedizinische Alternsforschung der Osterreichischen Akademie der Wissenschaften, Rennweg 10, A-6020, Innsbruck, Austria. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Aging
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physiology* Cell Cycle Proteins / genetics*, metabolism* Cells, Cultured Cyclin D1 / genetics, metabolism Cyclin-Dependent Kinase Inhibitor p21 Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases / antagonists & inhibitors* Cyclins / genetics, metabolism Fibroblasts / cytology, metabolism Gene Expression* Humans S-Phase Kinase-Associated Proteins Tumor Suppressor Proteins / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/CDKN1A protein, human; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/S-Phase Kinase-Associated Proteins; 0/Tumor Suppressor Proteins; 136601-57-5/Cyclin D1; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.11.22/Cyclin-Dependent Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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