title: Activity of the yeast zinc-finger transcription factor War1 is lost with alanine mutation of two putative phosphorylation sites in the activation domain.
abstract: Saccharomyces cerevisiae acquires its resistance to carboxylate weak organic acids by inducing a plasma membrane ABC transporter, Pdr12. These acids activate a Zn(II)2Cys6 zinc-finger transcription factor, War1, which in turn induces the PDR12 gene. Mutation of the four potential sites of serine/threonine phosphorylation within the War1 activation domain revealed that Pdr12 induction was lost with mutations S923A or S930A, but not with the corresponding phosphomimetic mutations S923D or S930D. However, phosphorylation at these two sites has not been detected by mass spectrometry, so it still remains uncertain whether these are true sites of phosphorylation or merely serines whose side-chain hydroxyls are necessary for the proper structuring of the War1 activation domain. Mutation S923A prevented the sorbate-induced hyperphosphorylation of War1, while S930A caused War1 to be in a constitutively hyperphosphorylated state, irrespective of weak acid stress. Screening of non-essential protein kinase mutants of yeast failed to identify a kinase required for Pdr12 induction, or War1 hyperphosphorylation, in response to sorbate treatment. However, the mrk1∆ mutant was identified as having an elevated Pdr12 level in the absence of sorbate stress.
authors: Department of Molecular Biology and Biotechnology, University of Sheffield, UK.
authors: Mehdi
authors: M
authors: Mollapour
authors: Peter W
authors: PW
authors: Piper
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D020816:Amino Acid Motifs; D015966:Gene Expression Regulation, Fungal; D020125:Mutation, Missense; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016335:Zinc Fingers
chemical_list: D018528:ATP-Binding Cassette Transporters; C472673:Pdr12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C472674:War1 protein, S cerevisiae