Proteasomal degradation of Rpn4 in Saccharomyces cerevisiae is critical for cell viability under stressed conditions.

Genetics
Xiaogang WangYouming Xie

Abstract

The proteasome homeostasis in Saccharomyces cerevisiae is regulated by a negative feedback loop in which the transcription factor Rpn4 induces the proteasome genes and is rapidly degraded by the assembled proteasome. In addition to the proteasome genes, Rpn4 regulates numerous other genes involved in a wide range of cellular pathways. Therefore, the Rpn4-proteasome negative feedback circuit not only controls proteasome abundance, but also gauges the expression of other Rpn4 target genes. Our previous work has shown that Rpn4-induced gene expression is critical for cell viability under stressed conditions. Here we investigate whether proteasomal degradation of Rpn4 is also important for cell survival in response to stress. To this end, we generate a stabilized Rpn4 mutant (Rpn4*) that retains its transcription activity. We find that expression of Rpn4* severely reduces cell viability in response to various genotoxic and proteotoxic agents. This detrimental effect can be eliminated by a point mutation that abolishes the transcription activity of Rpn4*, suggesting that overexpression of some Rpn4 target genes weakens the cell's ability to cope with stress. Moreover, we demonstrate that inhibition of Rpn4 degradation causes synthet...Continue Reading

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Citations

Oct 3, 2012·Genetics·Daniel FinleyPeter Kaiser
Oct 12, 2010·Journal of Molecular Cell Biology·Youming Xie
Sep 12, 2014·Biomolecules·Geetha Durairaj, Peter Kaiser
Oct 31, 2012·Molecular Aspects of Medicine·Niki ChondrogianniEfstathios S Gonos
Mar 5, 2014·Molecular Microbiology·Mehdi KabaniRonald Melki
Nov 12, 2013·Current Biology : CB·Jacob Stewart-OrnsteinHana El-Samad
Mar 8, 2019·ELife·Blake W TyeL Stirling Churchman
Jun 25, 2019·Frontiers in Molecular Biosciences·Richard S Marshall, Richard D Vierstra
Jan 1, 2021·The Journal of Cell Biology·Jeremy J Work, Onn Brandman
Nov 5, 2020·International Journal of Molecular Sciences·Daria S SpasskayaDmitry S Karpov
Jun 8, 2021·Applied Microbiology and Biotechnology·B A BrandtR Den Haan

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