Document Detail


The bZip transcription factor Cgap1p is involved in multidrug resistance and required for activation of multidrug transporter gene CgFLR1 in Candida glabrata.
MedLine Citation:
PMID:  17046176     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Transcriptional regulation in response to environmental challenges is crucial for survival of many organisms. In this study, we characterized structural and functional properties of CgAP1, a Saccharomyces cerevisiae YAP1 ortholog, which encodes a transcription factor involved in various stress responses. Deletion of CgAP1 led to decreased resistance to hydrogen peroxide, 4-nitroquinoline-N-oxide (4-NQO), benomyl, and cadmium chloride, which could be fully recovered by reintroduction of an intact CgAP1. CgAP1 was shown to function in S. cerevisiae as it restored the drug resistance of the yap1 mutant. Moreover, overexpression of CgAP1 in a S. cerevisiae wild-type strain increased its resistance to cycloheximide, 1,10-phenanthroline, 4-NQO, and fluconazole. Overexpression of CgAP1 also phenotypically suppressed the drug sensitivity of two Yap1p-regulated transporter mutants, Deltaatr1 and Deltaflr1, to diamide, 4-NQO, and cadmium. Northern blot analysis indicated that Cgap1p regulates the benomyl-induced expression of CgFLR1, a homolog of S. cerevisiae FLR1, which encodes a transporter of the major facilitator superfamily. In contrast to the S. cerevisiae flr1 mutant, deletion of CgFLR1 in C. glabrata only resulted in increased sensitivity to benomyl, diamide, and menadione, but not 4-NQO, cycloheximide, or fluconazole. Taken together, this report demonstrated that CgAP1 plays a critical role in response to various stresses in C. glabrata and reduces the stress through transcriptional activation of its target genes including CgFLR1.
Authors:
Kuang-Hua Chen; Taiga Miyazaki; Huei-Fung Tsai; John E Bennett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2006-08-24
Journal Detail:
Title:  Gene     Volume:  386     ISSN:  0378-1119     ISO Abbreviation:  Gene     Publication Date:  2007 Jan 
Date Detail:
Created Date:  2006-12-22     Completed Date:  2007-03-07     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7706761     Medline TA:  Gene     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  63-72     Citation Subset:  IM    
Affiliation:
Clinical Mycology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Basic-Leucine Zipper Transcription Factors / physiology*
Candida glabrata / genetics,  physiology*
Drug Resistance, Multiple, Fungal / genetics*
Female
Gene Expression Regulation, Fungal / physiology*
Membrane Transport Proteins / biosynthesis,  genetics,  physiology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data
Organic Anion Transporters
Saccharomyces cerevisiae Proteins / physiology
Chemical
Reg. No./Substance:
0/Basic-Leucine Zipper Transcription Factors; 0/FLR1 protein, S cerevisiae; 0/Membrane Transport Proteins; 0/Organic Anion Transporters; 0/Saccharomyces cerevisiae Proteins

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