Expression of a yeast metallothionein gene family is activated by a single metalloregulatory transcription factor.

TitleExpression of a yeast metallothionein gene family is activated by a single metalloregulatory transcription factor.
Publication TypeJournal Article
Year of Publication1992
AuthorsZhou P, Szczypka MS, Sosinowski T, Thiele DJ
JournalMol Cell Biol
Date Published1992 Sep
KeywordsAmino Acid Sequence, Base Sequence, Cadmium, Candida, Cloning, Molecular, Deoxyribonuclease I, DNA, Fungal, DNA-Binding Proteins, Drug Resistance, Microbial, Fungal Proteins, Gene Expression Regulation, Fungal, Metallothionein, Molecular Sequence Data, Multigene Family, Protein Binding, Restriction Mapping, Transcription Factors, Transcription, Genetic

The opportunistic pathogenic yeast Candida glabrata elicits at least two major responses in the presence of high environmental metal levels: transcriptional induction of the metallothionein gene family by copper and the appearance of small (gamma-Glu-Cys)nGly peptides in the presence of cadmium. On the basis of a trans-activation selection scheme in the baker's yeast Saccharomyces cerevisiae, we previously isolated a C. glabrata gene which encodes a copper-activated DNA-binding protein designated AMT1. AMT1 forms multiple specific DNA-protein complexes with both C. glabrata MT-I and MT-IIa promoter DNA fragments. In this report, we localize and define the AMT1-binding sites in the MT-I and MT-IIa promoters and characterize the mode of AMT1 binding. Furthermore, we demonstrate that the AMT1 protein trans activates both the MT-I and MT-IIa genes in vivo in response to copper and that this activation is essential for high-level copper resistance in C. glabrata. Although AMT1-mediated trans activation of the C. glabrata metallothionein genes is essential for copper resistance, AMT1 is completely dispensable for cadmium tolerance. The distinct function that metallothionein genes have in copper but not cadmium detoxification in C. glabrata is in contrast to the role that metallothionein genes play in tolerance to multiple metals in higher organisms.

Alternate JournalMol Cell Biol
PubMed ID1508182
PubMed Central IDPMC360240
Grant ListGM41840 / GM / NIGMS NIH HHS / United States
Related Faculty: 
Pengbo Zhou, Ph.D.

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