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Originally published In Press as doi:10.1074/jbc.M107131200 on August 14, 2001

J. Biol. Chem., Vol. 276, Issue 42, 38697-38702, October 19, 2001
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Haa1, a Protein Homologous to the Copper-regulated Transcription Factor Ace1, Is a Novel Transcriptional Activator*

Greg KellerDagger , Esha Ray§, Patrick O. Brown§, and Dennis R. WingeDagger ||

From the Dagger  University of Utah Health Sciences Center, Departments of Medicine and Biochemistry, Salt Lake City, Utah 84132 and the § Department of Biochemistry, Stanford University School of Medicine, Howard Hughes Medical Institute, Stanford, California 94305-5428

The Saccharomyces cerevisiae genome contains a predicted gene, YPR008w, homologous to the gene encoding the copper-activated transcription factor Ace1. The product of the YPR008w gene, designated Haa1, regulates the transcription of a set of yeast genes, many of which encode membrane proteins. Two main target genes of Haa1 are the multidrug resistance gene YGR138c and the YRO2 homolog to the plasma membrane Hsp30. Haa1 is localized to the nucleus. Haa1-induced expression of YGR138c and YRO2 appears to be direct. Induction of HAA1 using a GAL1/HAA1 fusion gene resulted in rapid galactose-induced expression of both HAA1 and target genes. Although Haa1 has a sequence very similar to the Cu-activated DNA binding domain of Ace1, expression of Haa1 target genes was found to be independent of the copper status of cells. Haa1 does not exhibit metalloregulation in cells incubated with a range of transition metal salts. Haa1 does not exhibit any cross-talk with Ace1. Overexpression of Haa1 does not compensate for cells lacking a functional Ace1. The lack of metalloregulation of Haa1 despite the strong sequence similarity to the copper regulatory domain of Ace1 is discussed.

* This work was supported by Grants ES03817 and CA 61286 from the NIEHS and NCI, National Institutes of Health (to D. R. W.) and Grant G00983 (to P. O. B.) We acknowledge support from the National Institutes of Health (Grant 5P30-CA 42014) to the Biotechnology Core Facility for DNA synthesis at the University of Utah and acknowledge technical assistance of the University of Utah Microarray Core Facility led by Dr. Brian Dalley and supported by the Huntsmann Cancer Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Associate investigator of the Howard Hughes Medical Institute.

|| To whom correspondence should be addressed. Tel.: 801-585-5103; Fax: 801-585-5469; E-mail: dennis.winge@hsc.utah.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


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Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.