Homeostatic regulation of the proteasome via an Rpn4-dependent feedback circuit

Biochemical and Biophysical Research Communications
Donghong JuY Xie

Abstract

The 26S proteasome is a complex protease consisting of at least 32 different subunits. Early studies showed that Rpn4 (also named Son1 and Ufd5) is a transcriptional activator of the Saccharomyces cerevisiae proteasome genes, and that Rpn4 is rapidly degraded by the 26S proteasome. These observations suggested that in vivo proteasome abundance may be regulated by an Rpn4-dependent feedback circuit. Here, we present direct evidence to support the Rpn4-proteasome feedback model. We show that proteasome expression is increased when proteasome activity is impaired, and that this increase is Rpn4-dependent. Moreover, we demonstrate that expression of a stable form of Rpn4 leads to elevation of proteasome expression. Our data also reveal that the Rpn4-proteasome feedback circuit is critical for cell growth when proteasome activity is compromised, and plays an important role in response to DNA damage. This study provides important insights into the mechanism underlying proteasome homeostasis.

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Citations

Sep 15, 2005·Molecular Genetics and Genomics : MGG·D A MacKenzieD B Archer
Oct 17, 2008·Biogerontology·Alan R Hipkiss
Oct 12, 2010·Journal of Molecular Cell Biology·Youming Xie
Mar 10, 2010·Biochemistry. Biokhimii︠a︡·A V SorokinL P Ovchinnikov
Aug 16, 2008·Molekuliarnaia biologiia·D S KarpovV L Karpov
May 12, 2009·Molekuliarnaia biologiia·D S KarpovV L Karpov
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Dec 6, 2011·Mutation Research·Chunlan YanJun Yang
Nov 17, 2009·The International Journal of Biochemistry & Cell Biology·Donghong JuYouming Xie
Sep 11, 2007·Biochimie·Jasmina Kurepa, Jan A Smalle
May 19, 2011·The EMBO Journal·Nikos Kourtis, Nektarios Tavernarakis
Jan 25, 2006·Biochemical and Biophysical Research Communications·Donghong Ju, Youming Xie
Sep 3, 2013·Biochimica Et Biophysica Acta·Marion Schmidt, Daniel Finley
Mar 20, 2013·Biochimica Et Biophysica Acta·Mary J Kunjappu, Mark Hochstrasser
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Oct 27, 2004·The Journal of Biological Chemistry·Li WangYouming Xie
Feb 24, 2006·The Journal of Biological Chemistry·Donghong Ju, Youming Xie
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Apr 26, 2014·The Journal of Biological Chemistry·Alexander N PatanananSteven G Clarke
Oct 24, 2020·Scientific Reports·Kenrick A WaiteJeroen Roelofs
Aug 5, 2021·Molecular Biology of the Cell·Chin Leng ChengMark Hochstrasser

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