title: Regulation of Schizosaccharomyces pombe Atf1 protein levels by Sty1-mediated phosphorylation and heterodimerization with Pcr1.
abstract: The Atf1 transcription factor plays a vital role in the ability of Schizosaccharomyces pombe cells to respond to various stress conditions. It regulates the expression of many genes in a stress-dependent manner, and its function is dependent upon the stress-activated MAPK, Sty1/Spc1. Moreover, Atf1 is directly phosphorylated by Sty1. Here we have investigated the role of such phosphorylation. Atf1 protein accumulates following stress, and this accumulation is lost in a strain defective in the Sty1 signaling pathway. In addition, accumulation of a mutant Atf1 protein that can no longer be phosphorylated is lost. Measurement of the half-life of Atf1 demonstrates that changes in Atf1 stability are responsible for this accumulation. Atf1 stability is also regulated by its heterodimeric partner, Pcr1. Similarly, Pcr1 levels are regulated by Atf1. Thus multiple pathways exist that ensure that Atf1 levels are appropriately regulated. Phosphorylation of Atf1 is important for cells to mount a robust response to H(2)O(2) stress, because the Atf1 phospho-mutant displays sensitivity to this stress, and induction of gene expression is lower than that observed in wild-type cells. Surprisingly, however, loss of Atf1 phosphorylation does not lead to the complete loss of stress-activated expression of Atf1 target genes. Accordingly, the Atf1 phospho-mutant does not display the same overall stress sensitivities as the atf1 deletion mutant. Taken together, these data suggest that Sty1 phosphorylation of Atf1 is not required for activation of Atf1 per se but rather for modulating its stability.
authors.affiliation: Cancer Research UK Cell Regulation Laboratory, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, United Kingdom.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Lawrence
authors.forename: Hiromi
authors.initials: H
authors.lastname: Maekawa
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Worthington
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Reiter
authors.forename: Caroline R M
authors.initials: CR
authors.lastname: Wilkinson
authors.forename: Nic
authors.initials: N
authors.lastname: Jones
mesh_terms: D051697:Activating Transcription Factor 1 / Q000235:genetics / Q000378:metabolism*; D051696:Activating Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects / Q000235:genetics; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009997:Osmotic Pressure / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D013012:Sorbitol / Q000494:pharmacology; D013549:Sweetening Agents / Q000494:pharmacology
chemical_list: D051697:Activating Transcription Factor 1; D051696:Activating Transcription Factors; D016877:Oxidants; C097701:Pcr1 protein, S pombe; D010750:Phosphoproteins; D029702:Schizosaccharomyces pombe Proteins; D013549:Sweetening Agents; C106740:atf1 protein, S pombe; D013012:Sorbitol; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe