Book chapter
Chapter 17 Oxidant-specific protein folding during fungal oxidative stress: Activation and function of the yaplp transcription factor in Saccharomyces cerevisiae
British Mycological Society Symposia Series, pp.275-290
Elsevier Science & Technology
2008
DOI: 10.1016/S0275-0287(08)80059-8
Abstract
Fungal cells are eliminated from animal hosts through oxidative stressmediated mechanisms. The ability to tolerate oxidative stress has been correlated with virulence in pathogenic fungi like Candida and Aspergillus species. The yeast Saccharomyces cerevisiae has served as an excellent model system for both fungal oxidative stress tolerance in particular and eukaryotic oxidant detoxification in general. A central determinant of oxidative-stress resistance in S. cerevisiae is the transcriptional activator protein Yaplp. Yaplp is normally found in the cytoplasm in the absence of oxidative stress but rapidly recruits to the nucleus upon challenge by oxidants such as H202 or diamide. Detailed mutagenesis and functional studies have demonstrated that two different cysteine-rich domains (CRDs) present in Yaplp are involved in detecting and responding to changes in the redox potential of the cell. The carboxy-terminal CRD (c-CRD) is sufficient to provide diamide regulation of nuclear localization to a chimeric green fluorescent protein (GFP) reporter fusion and contains an important nuclear export signal of Yaplp. Biochemical analyses have provided evidence that different folding states of Yaplp are found during diamide or H202 exposure. In the context of wild-type Yaplp, a second amino-terminal CRD (n-CRD) is required for normal regulation and function of Yaplp in response to H2O2 induced oxidative stress. Unlike the situation during diamide stress, correct folding of Yaplp in the presence of H2O2 requires the presence of ancillary factors like the glutathione peroxidase Gpx3p and the Yaplp-interacting protein Ybplp. While regulation of the nuclear export of Yaplp is a key modulatory step during both diamide and H2O2 induced oxidative stress, recent experiments have shown that a second feature of the H2O2 folded state of Yaplp is required to assure normal function in the presence of this oxidant. This review will summarize the state of understanding of oxidant-specific folding of Yaplp and the requirement for the folded state of Yaplp that is generated in the presence of H2O2 during the response to this oxidant.
Details
- Title: Subtitle
- Chapter 17 Oxidant-specific protein folding during fungal oxidative stress: Activation and function of the yaplp transcription factor in Saccharomyces cerevisiae
- Creators
- W. Scott Moye-Rowley
- Resource Type
- Book chapter
- Publication Details
- British Mycological Society Symposia Series, pp.275-290
- Publisher
- Elsevier Science & Technology
- DOI
- 10.1016/S0275-0287(08)80059-8
- ISSN
- 0275-0287
- Language
- English
- Date published
- 2008
- Academic Unit
- Molecular Physiology and Biophysics; Internal Medicine
- Record Identifier
- 9984297609802771
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