Interaction of Gcn4 with target gene chromatin is modulated by proteasome function.

Howard GC, Tansey WP
Mol Biol Cell. 2016 27 (17): 2735-41

PMID: 27385344 · PMCID: PMC5007093 · DOI:10.1091/mbc.E16-03-0192

The ubiquitin-proteasome system (UPS) influences gene transcription in multiple ways. One way in which the UPS affects transcription centers on transcriptional activators, the function of which can be stimulated by components of the UPS that also trigger their destruction. Activation of transcription by the yeast activator Gcn4, for example, is attenuated by mutations in the ubiquitin ligase that mediates Gcn4 ubiquitylation or by inhibition of the proteasome, leading to the idea that ubiquitin-mediated proteolysis of Gcn4 is required for its activity. Here we probe the steps in Gcn4 activity that are perturbed by disruption of the UPS. We show that the ubiquitylation machinery and the proteasome control different steps in Gcn4 function and that proteasome activity is required for the ability of Gcn4 to bind to its target genes in the context of chromatin. Curiously, the effect of proteasome inhibition on Gcn4 activity is suppressed by mutations in the ubiquitin-selective chaperone Cdc48, revealing that proteolysis per se is not required for Gcn4 activity. Our data highlight the role of Cdc48 in controlling promoter occupancy by Gcn4 and support a model in which ubiquitylation of activators-not their destruction-is important for function.

© 2016 Howard and Tansey. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (

MeSH Terms (15)

Adenosine Triphosphatases Basic-Leucine Zipper Transcription Factors Cell Cycle Proteins Chromatin DNA-Binding Proteins Molecular Chaperones Proteasome Endopeptidase Complex Proteolysis Saccharomyces cerevisiae Saccharomyces cerevisiae Proteins Transcriptional Activation Transcription Factors Ubiquitin Ubiquitination Valosin Containing Protein

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