Arsenic Directly Binds to and Activates the Yeast AP-1-Like Transcription Factor Yap8
The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeast Saccharomyces cerevisiae . However, the mechanism by which Yap8 senses the presence of arsenic and activates transcription of detoxification genes is unknown. Here we demonstrate that Yap8 directly binds to trival...
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Published in | Molecular and cellular biology Vol. 36; no. 6; pp. 913 - 922 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Taylor & Francis
01.03.2016
American Society for Microbiology |
Subjects | |
Online Access | Get full text |
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Summary: | The AP-1-like transcription factor Yap8 is critical for arsenic tolerance in the yeast
Saccharomyces cerevisiae
. However, the mechanism by which Yap8 senses the presence of arsenic and activates transcription of detoxification genes is unknown. Here we demonstrate that Yap8 directly binds to trivalent arsenite [As(III)] in vitro and in vivo and that approximately one As(III) molecule is bound per molecule of Yap8. As(III) is coordinated by three sulfur atoms in purified Yap8, and our genetic and biochemical data identify the cysteine residues that form the binding site as Cys132, Cys137, and Cys274. As(III) binding by Yap8 does not require an additional yeast protein, and Yap8 is regulated neither at the level of localization nor at the level of DNA binding. Instead, our data are consistent with a model in which a DNA-bound form of Yap8 acts directly as an As(III) sensor. Binding of As(III) to Yap8 triggers a conformational change that in turn brings about a transcriptional response. Thus, As(III) binding to Yap8 acts as a molecular switch that converts inactive Yap8 into an active transcriptional regulator. This is the first report to demonstrate how a eukaryotic protein couples arsenic sensing to transcriptional activation. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22) BNL-112785-2016-JA SC00112704 Citation Kumar NV, Yang J, Pillai JK, Rawat S, Solano C, Kumar A, Grøtli M, Stemmler TL, Rosen BP, Tamás MJ. 2016. Arsenic directly binds to and activates the yeast AP-1-like transcription factor Yap8. Mol Cell Biol 36:913–922. doi:10.1128/MCB.00842-15. |
ISSN: | 1098-5549 0270-7306 1098-5549 |
DOI: | 10.1128/MCB.00842-15 |