SCFCdc4-mediated degradation of the Hac1p transcription factor regulates the unfolded protein response in Saccharomyces cerevisiae

Pal, B., Chan, N. C., Helfenbaum, L., Tan, K. L., Tansey, W. P., Gething, M. J. (February 2007) SCFCdc4-mediated degradation of the Hac1p transcription factor regulates the unfolded protein response in Saccharomyces cerevisiae. Molecular Biology of the Cell, 18 (2). pp. 426-440. ISSN 1059-1524

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URL: https://www.ncbi.nlm.nih.gov/pubmed/17108329
DOI: 10.1091/mbc.E06-04-0304

Abstract

The Saccharomyces cerevisiae basic leucine zipper transcription factor Hac1p is synthesized in response to the accumulation of unfolded polypeptides in the lumen of the endoplasmic reticulum (ER), and it is responsible for up-regulation of similar to 5% of all yeast genes, including ER-resident chaperones and protein-folding catalysts. Hac1p is one of the most short-lived yeast proteins, having a half-life of similar to 1.5 min. Here, we have shown that Hac1p harbors a functional PEST degron and that degradation of Hac1p by the proteasome involves the E2 ubiquitin-conjugating enzyme Ubc3/Cdc34p and the SCFCdc4 E3 complex. Consistent with the known nuclear localization of Cdc4p, rapid degradation of Hac1p requires the presence of a functional nuclear localization sequence, which we demonstrated to involve basic residues in the sequence (29)RKRAKTK(35). Two-hybrid analysis demonstrated that the PEST-dependent interaction of Hac1p with Cdc4p requires Ser146 and Ser149. Turnover of Hac1p may be dependent on transcription because it is inhibited in cell mutants lacking Srb10 kinase, a component of the SRB/mediator module of the RNA polymerase II holoenzyme. Stabilization of Hac1p by point mutation or deletion, or as the consequence of defects in components of the degradation pathway, results in increased unfolded protein response element-dependent transcription and improved cell viability under ER stress conditions.

Item Type: Paper
Uncontrolled Keywords: UBIQUITIN-DEPENDENT PROTEOLYSIS ENDOPLASMIC-RETICULUM PROTEIN CELL-CYCLE BUDDING YEAST KINASE-C F-BOX MULTISITE PHOSPHORYLATION TRANSMEMBRANE PROTEIN MEDIATED PROTEOLYSIS STRUCTURAL BASIS
Subjects: organism description > yeast > Saccharomyces
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:
Communities: CSHL labs > Tansey lab
Depositing User: CSHL Librarian
Date: February 2007
Date Deposited: 07 Nov 2011 20:24
Last Modified: 02 Apr 2018 20:26
PMCID: PMC1783797
Related URLs:
URI: http://repository.cshl.edu/id/eprint/23116

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