Cadmium tolerance mediated by the yeast AP-1 protein requires the presence of an ATP-binding cassette transporter-encoding gene, YCF1

John A Wemmie; Mark S Szczypka; Dennis J Thiele; W Scott Moye-Rowley

doi:10.1016/S0021-9258(18)31675-2

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Cadmium tolerance mediated by the yeast AP-1 protein requires the presence of an ATP-binding cassette transporter-encoding gene, YCF1

Journal article

Open access

Peer reviewed

Cadmium tolerance mediated by the yeast AP-1 protein requires the presence of an ATP-binding cassette transporter-encoding gene, YCF1

John A Wemmie, Mark S Szczypka, Dennis J Thiele and W Scott Moye-Rowley

The Journal of biological chemistry, Vol.269(51), pp.32592-32597

12/23/1994

DOI: 10.1016/S0021-9258(18)31675-2

PMID: 7798263

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Abstract

Elevations in gene dosage of the transcriptional regulatory protein yAP-1 in Saccharomyces cerevisiae can elicit pronounced phenotypic increases in tolerance of a variety of drugs including the toxic heavy metal cadmium. While a large elevation in cadmium tolerance occurs in response to overproduction of yAP-1, the target genes under yAP-1 control have not yet been identified that are responsible for this increase. We show here that the YCF1 gene, encoding a likely integral membrane protein, is required for yAP-1 to exert its normal effects on cadmium tolerance. Mutant strains of yeast that lack the YCF1 gene are hypersensitive to cadmium and this hypersensitivity is epistatic to yAP-1 overexpression. YCF1 mRNA levels and the expression of a YCF1-lacZ reporter construct positively correlates with changes in YAP1 gene dosage. A set of 5' truncation derivatives of the YCF1-lacZ fusion gene identified the region from -201 to +47 as being sufficient for the yAP-1-dependent increase in expression. DNase I footprinting using a probe from this segment of the YCF1 promoter showed that bacterially-produced yAP-1 protein was capable of binding a novel DNA element we have designated the yAP-1 response element. Insertion of the yAP-1 response element upstream of a CYC1-lacZ gene fusion led to the production of beta-galactosidase in a yAP-1-dependent fashion. These data establish that an important physiological target of yAP-1 transcriptional regulation is the YCF1 structural gene.

Promoter Regions, Genetic

Cadmium - toxicity

Molecular Sequence Data

Gene Dosage

Fungal Proteins - genetics

DNA, Fungal

RNA, Messenger - metabolism

Sequence Homology, Nucleic Acid

Transcription Factor AP-1 - metabolism

Saccharomyces cerevisiae - metabolism

Drug Resistance, Microbial

ATP-Binding Cassette Transporters

Base Sequence

Saccharomyces cerevisiae Proteins

Transcription, Genetic

Details

Title: Subtitle: Cadmium tolerance mediated by the yeast AP-1 protein requires the presence of an ATP-binding cassette transporter-encoding gene, YCF1
Creators: John A Wemmie - Department of Physiology and Biophysics, University of Iowa, Iowa City 52242
Mark S Szczypka
Dennis J Thiele
W Scott Moye-Rowley
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.269(51), pp.32592-32597
DOI: 10.1016/S0021-9258(18)31675-2
PMID: 7798263
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: GM25295 / NIGMS NIH HHS GM49825 / NIGMS NIH HHS
Language: English
Date published: 12/23/1994
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Neurosurgery; Internal Medicine
Record Identifier: 9984003960102771

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