A novel transcription factor, War1p, mediates adaptation to weak acid
stress by controlling expression of the yeast Pdr12p ATP-binding
cassette (ABC) transporter.
Yasmine Mamnun (1), Angelika Kren
(1), Bettina Bauer (1), Christoph Schüller (1), Chantal Schwartz (1),
Mehdi Mollapour (2), Peter Piper (2), Karl Kuchler (3)
(1)
Institute Medical Biochemistry, Vienna BioCenter, Dr. Bohr-Gasse 9/2,
Vienna, A-1030, Austria; (2) University College London, Department of
Biochemistry & Molecular Biology, Gower Street, London WC1E 6BT, United
Kingdom; (3) Institute of Medical Biochemistry, University & 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@mol.univie.ac.at
The
S. cerevisiae genome harbors 30 genes encoding ATP-binding
cassette (ABC) proteins. We demonstrated that the Pdr12p ABC pump
mediates resistance to carboxylate anions such as sorbate and benzoate,
and that PDR12 is tightly regulated by adverse conditions such
weak acid stress. However, specific regulators have not been identified.
We have thus employed a genetic screen to isolate mutants displaying
increased weak acid sensitivity. In addition, we screened the deletion
collection to identify genes mediating weak acid tolerance. Finally,
transcriptome analysis using DNA microarrays established a subset of
genes involved in weak acid stress adaptation. Taken together, our work
uncovered a novel transcriptional regulator, War1p, which is required
for the induction of PDR12 after stress exposure. War1p
constitutively localizes to the nucleus, and becomes rapidly
phosphorylated and perhaps activated upon stress challenge. The
PDR12 induction is controlled through a novel cis-acting
element, the weak acid response element (WARE). In
vivofootprinting experiments and promoter deletions identified and
demonstrated the existence of three distinct WAREs in the PDR12
promoter, at least two of which are necessary and sufficient for
PDR12 expression regulation. The War1p transcription factor
controls a rather small but distinct weak acid response regulon
dedicated to weak organic acid stress adaptation. War1p represents the
first stress-specific regulator for a eukaryotic ABC gene.
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