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Molecular and Cellular Biology, March 2003, p. 1775-1785, Vol. 23, No. 5
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.5.1775-1785.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

War1p, a Novel Transcription Factor Controlling Weak Acid Stress Response in Yeast

Angelika Kren,1 Yasmine M. Mamnun,1 Bettina E. Bauer,1 Christoph Schüller,1 Hubert Wolfger,1 Kostas Hatzixanthis,2 Mehdi Mollapour,2 Christa Gregori,1 Peter Piper,2 and Karl Kuchler1*

Department of Molecular Genetics, Institute of Medical Biochemistry, University and BioCenter of Vienna, A-1030 Vienna, Austria,1 Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom2

Received 9 September 2002/ Returned for modification 22 October 2002/ Accepted 13 December 2002

The Saccharomyces cerevisiae ATP-binding cassette (ABC) transporter Pdr12p effluxes weak acids such as sorbate and benzoate, thus mediating stress adaptation. In this study, we identify a novel transcription factor, War1p, as the regulator of this stress adaptation through transcriptional induction of PDR12. Cells lacking War1p are weak acid hypersensitive, since they fail to induce Pdr12p. The nuclear Zn2Cys6 transcriptional regulator War1p forms homodimers and is rapidly phosphorylated upon sorbate stress. The appearance of phosphorylated War1p isoforms coincides with transcriptional activation of PDR12. Promoter deletion analysis identified a novel cis-acting weak acid response element (WARE) in the PDR12 promoter required for PDR12 induction. War1p recognizes and decorates the WARE both in vitro and in vivo, as demonstrated by band shift assays and in vivo footprinting. Importantly, War1p occupies the WARE in the presence and absence of stress, demonstrating constitutive DNA binding in vivo. Our results suggest that weak acid stress triggers phosphorylation and perhaps activation of War1p. In turn, War1p activation is necessary for the induction of PDR12 through a novel signal transduction event that elicits weak organic acid stress adaptation.

* Corresponding author. Mailing address: Institute of Medical Biochemistry, Department of Molecular Genetics, University and BioCenter of Vienna, Dr. Bohr-Gasse 9/2, A-1030 Vienna, Austria. Phone: 43-1-4277-61807. Fax: 43-1-4277-9618. E-mail: kaku{at}mol.univie.ac.at.

Molecular and Cellular Biology, March 2003, p. 1775-1785, Vol. 23, No. 5
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.5.1775-1785.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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