The Library
Overexpression of proteasome 5 assembled subunit increases the amount of proteasome and confers ameliorated response to oxidative stress and higher survival rates
Tools
Chondrogianni, N., Tzavelas, C., Pemberton, A. J., Nezis, I. P., Rivett, A. J. and Gonos, E. S. (2005) Overexpression of proteasome 5 assembled subunit increases the amount of proteasome and confers ameliorated response to oxidative stress and higher survival rates. Journal of Biological Chemistry, Volume 280 (Number 12). pp. 11840-11850. doi:10.1074/jbc.M413007200 ISSN 0021-9258.
Research output not available from this repository.
Request-a-Copy directly from author or use local Library Get it For Me service.
Official URL: http://dx.doi.org/10.1074/jbc.M413007200
Abstract
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 β-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 β5 subunit. Stable overexpression of the β5 subunit in WI38/T and HL60 cells resulted in elevated levels of other β-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) α-type subunits identified to accumulate in vector-transfected cells. In support we have also found low proteasome maturation protein levels in β5 transfectants, thus revealing an increased rate/level of proteasome assembly in these cells as opposed to vector-transfected cells. Functional studies have shown that β5-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 β5 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.
Item Type: | Journal Article | ||||
---|---|---|---|---|---|
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Journal or Publication Title: | Journal of Biological Chemistry | ||||
Publisher: | American Society for Biochemistry and Molecular Biology | ||||
ISSN: | 0021-9258 | ||||
Official Date: | 20 January 2005 | ||||
Dates: |
|
||||
Volume: | Volume 280 | ||||
Number: | Number 12 | ||||
Page Range: | pp. 11840-11850 | ||||
DOI: | 10.1074/jbc.M413007200 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access |
Request changes or add full text files to a record
Repository staff actions (login required)
View Item |