Journal article
Proteolytic Degradation of the Yap1 Transcription Factor Is Regulated by Subcellular Localization and the E3 Ubiquitin Ligase Not4
The Journal of biological chemistry, Vol.287(32), pp.26796-26805
08/03/2012
DOI: 10.1074/jbc.M112.384719
PMCID: PMC3411017
PMID: 22707721
Abstract
Saccharomyces cerevisiae Yap1 is a transcriptional regulatory protein that serves as a central determinant of oxidative stress tolerance. Activity of this factor is regulated in large part by control of its subcellular location. In the absence of oxidants, Yap1 is primarily located in the cytoplasm. Upon oxidant challenge, Yap1 accumulates rapidly in the nucleus where it activates expression of genes required for oxidative stress tolerance such as the thioredoxin TRX2. Here, we demonstrate that Yap1 degradation is accelerated in response to oxidative stress. Yap1 is folded differently depending on the oxidant used to induce its nuclear localization but is degraded similarly, irrespective of its folded status. Mutant forms of Yap1 that are constitutively trapped in the nucleus are degraded in the absence of an oxidant signal. Degradation requires the ability of the protein to bind DNA and a domain in the amino-terminal region of the factor. Inhibition of the proteasome prevents Yap1 turnover. Screening a variety of mutants involved in ubiquitin-mediated proteolysis demonstrated an important role for the nuclear ubiquitin ligase Not4 in Yap1 degradation. Not4 was found to bind to Yap1 in an oxidant-stimulated fashion. The Candida albicans Yap1 homologue (Cap1) also was degraded after oxidant challenge. These data uncover a new, conserved pathway for regulation of the oxidative stress response that serves to temporally limit the duration of Yap1-dependent transcriptional activation.
Details
- Title: Subtitle
- Proteolytic Degradation of the Yap1 Transcription Factor Is Regulated by Subcellular Localization and the E3 Ubiquitin Ligase Not4
- Creators
- Kailash Gulshan - Roy J. and Lucille A. Carver College of MedicineBernice Thommandru - Roy J. and Lucille A. Carver College of MedicineW. Scott Moye-Rowley - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.287(32), pp.26796-26805
- DOI
- 10.1074/jbc.M112.384719
- PMID
- 22707721
- PMCID
- PMC3411017
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 10
- Grant note
- GM49825 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01GM049825 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS)
- Language
- English
- Date published
- 08/03/2012
- Academic Unit
- Molecular Physiology and Biophysics; Internal Medicine
- Record Identifier
- 9984297508002771
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