| Overexpression of proteasome beta5 assembled subunit increases the amount of proteasome and confers ameliorated response to oxidative stress and higher survival rates. | |
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MedLine Citation:
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PMID: 15661736 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The proteasome is the major cellular proteolytic machinery responsible for the degradation of both normal and damaged proteins. Proteasomes play a fundamental role in retaining cellular homeostasis. Alterations of proteasome function have been recorded in various biological phenomena including aging. We have recently shown that the decrease in proteasome activity in senescent human fibroblasts relates to the down-regulation of beta-type subunits. In this study we have followed our preliminary observation by developing and further characterizing a number of different human cell lines overexpressing the beta5 subunit. Stable overexpression of the beta5 subunit in WI38/T and HL60 cells resulted in elevated levels of other beta-type subunits and increased levels of all three proteasome activities. Immunoprecipitation experiments have shown increased levels of assembled proteasomes in stable clones. Analysis by gel filtration has revealed that the recorded higher level of proteasome assembly is directly linked to the efficient integration of "free" (not integrated) alpha-type subunits identified to accumulate in vector-transfected cells. In support we have also found low proteasome maturation protein levels in beta5 transfectants, thus revealing an increased rate/level of proteasome assembly in these cells as opposed to vector-transfected cells. Functional studies have shown that beta5-overexpressing cell lines confer enhanced survival following treatment with various oxidants. Moreover, we demonstrate that this increased rate of survival is due to higher degradation rates following oxidative stress. Finally, because oxidation is considered to be a major factor that contributes to aging and senescence, we have overexpressed the beta5 subunit in primary IMR90 human fibroblasts and observed a delay of senescence by 4-5 population doublings. In summary, these data demonstrate the phenotypic effects following genetic up-regulation of the proteasome and provide insights toward a better understanding of proteasome regulation. |
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Authors:
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Niki Chondrogianni; Christos Tzavelas; Alexander J Pemberton; Ioannis P Nezis; A Jennifer Rivett; Efstathios S Gonos |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-01-20 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 280 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2005 Mar |
Date Detail:
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Created Date: 2005-03-21 Completed Date: 2005-04-21 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 11840-50 Citation Subset: IM |
Affiliation:
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National Hellenic Research Foundation, Institute of Biological Research and Biotechnology, 48 Vasileos Constantinou Avenue, Athens 116 35, Greece. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Catalytic Domain Cell Aging Cell Survival Fibroblasts / physiology HL-60 Cells Humans Oxidative Stress* Proteasome Endopeptidase Complex / analysis, chemistry, genetics, physiology* Protein Subunits |
| Chemical | |
Reg. No./Substance:
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0/Protein Subunits; EC 3.4.25.1/Proteasome Endopeptidase Complex |
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