Repression of sulfate assimilation is an adaptive response of yeast to the oxidative stress of zinc deficiency.
The Zap1 transcription factor is a central player in the response of yeast to changes in zinc status. Previous studies identified over 80 genes activated by Zap1 in zinc-limited cells. In this report, we identified 36 genes repressed in a zinc- and Zap1-responsive manner. As a result, we have identified a new mechanism of Zap1-mediated gene repression whereby transcription of the MET3, MET14, and MET16 genes is repressed in zinc-limited cells. These genes encode the first three enzymes of the sulfate assimilation pathway. We found that MET30, encoding a component of the SCF(Met30) ubiquitin ligase, is a direct Zap1 target gene. MET30 expression is increased in zinc-limited cells, and this leads to degradation of Met4, a transcription factor responsible for MET3, MET14, and MET16 expression. Thus, Zap1 is responsible for a decrease in sulfate assimilation in zinc-limited cells. We further show that cells that are unable to down-regulate sulfate assimilation under zinc deficiency experience increased oxidative stress. This increased oxidative stress is associated with an increase in the NADP(+)/NADPH ratio and may result from a decrease in NADPH-dependent antioxidant activities. These studies have led to new insights into how cells adapt to nutrient-limiting growth conditions.
Wu
Chang-Yi
CY
Department of Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706, USA.
Roje
Sanja
S
Sandoval
Francisco J
FJ
Bird
Amanda J
AJ
Winge
Dennis R
DR
Eide
David J
DJ
D000222:Adaptation, Physiological; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism; D015536:Down-Regulation; D044783:F-Box Proteins / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism*; D013455:Sulfur / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D025801:Ubiquitin / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics; D015032:Zinc / Q000172:deficiency*
D050976:Basic-Leucine Zipper Transcription Factors; D044783:F-Box Proteins; C470285:MET30 protein, S cerevisiae; C073675:MET4 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013431:Sulfates; D014157:Transcription Factors; D025801:Ubiquitin; C103264:ZAP1 protein, S cerevisiae; D009249:NADP; D013455:Sulfur; D043743:Ubiquitin-Protein Ligase Complexes; D046988:Proteasome Endopeptidase Complex; D015032:Zinc