Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 275, Issue 41, Pages 32310-32316Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M005946200
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- NCI NIH HHS [CA61286, 5P30-CA 42014] Funding Source: Medline
- NHGRI NIH HHS [HG00983] Funding Source: Medline
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In Saccharomyces cerevisiae, copper ions regulate gene expression through the two transcriptional activators, Ace1 and Mad. Ace1 mediates copper-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mad activates a subset of genes under copper-deficient conditions. DNA microarray hybridization experiments revealed a limited set of yeast genes differentially expressed under growth conditions of excess copper or copper deficiency. Mad activates the expression of six S. cerevisiae genes, including CTR1, CTR3, FRE1, FRE7, YFR055w, and YJL217w, Two of the last three newly identified Mad target genes have no known function; the third, YFR055w, is homologous to cystathionine gamma-lyase encoded by CYS3. Several genes that are differentially expressed in cells containing a constitutively active Mad, designated Mac1(up1), are not direct targets of Mad. Induction or repression of these genes is likely a secondary effect of cells because of constitutive Mad activity. Elevated copper levels induced the expression of the metallothioneins CUP1 and CRS5 and two genes, FET3 and FTR1, in the iron uptake system. Copper-induced FET3 and FTR1 expression arises from an indirect copper effect on cellular iron pools.
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