Journal article
Differential Oxidant Tolerance Determined by the Key Transcription Factor Yap1 Is Controlled by Levels of the Yap1-binding Protein, Ybp1
The Journal of biological chemistry, Vol.286(39), pp.34071-34081
09/30/2011
DOI: 10.1074/jbc.M111.251298
PMCID: PMC3190762
PMID: 21844193
Abstract
The Saccharomyces cerevisiae transcription factor Yap1 is a central determinant of oxidative stress tolerance. This protein is found primarily in the cytoplasm in the absence of oxidative stress but, upon exposure to oxidants, rapidly translocates to the nucleus and activates expression of target genes. Although both diamide and H2O2 have been used to impose oxidative stress on cells, these different oxidants trigger Yap1 nuclear localization in distinctly different ways. Diamide appears to oxidize particular cysteine residues on Yap1, leading to inhibition of association of Yap1 with the nuclear exportin Crm1. Crm1 would normally transport Yap1 out of the nucleus. H2O2 activation of Yap1 nuclear localization requires the participation of the glutathione peroxidase Gpx3 and the Yap1-binding protein Ybp1. H2O2 exposure triggers formation of a dual disulfide bonded Yap1 that is catalyzed by the presence of Gpx3 and Ybp1. In the current study, we have determined that two distinct pools of Yap1 exist in the cell. These pools are designated by the level of Ybp1. Ybp1 interacts directly with Yap1 and these proteins form a stable complex in vivo. Genetic and biochemical experiments indicate that Ybp1 is rate-limiting for Yap1 oxidative folding during H2O2 stress. The fungal pathogen Candida glabrata expresses a protein homologous to Ybp1 called CgYbp1. Overproduction of CgYbp1 elevated H2O2 tolerance in this pathogen indicating that the determinative role of Ybp1 in setting the level of H2O2 resistance has been evolutionarily conserved.
Details
- Title: Subtitle
- Differential Oxidant Tolerance Determined by the Key Transcription Factor Yap1 Is Controlled by Levels of the Yap1-binding Protein, Ybp1
- Creators
- Kailash Gulshan - Roy J. and Lucille A. Carver College of MedicineStella S. Lee - 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.286(39), pp.34071-34081
- DOI
- 10.1074/jbc.M111.251298
- PMID
- 21844193
- PMCID
- PMC3190762
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 11
- 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
- 09/30/2011
- Academic Unit
- Molecular Physiology and Biophysics; Internal Medicine
- Record Identifier
- 9984297508202771
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