title: Sin1: an evolutionarily conserved component of the eukaryotic SAPK pathway.
abstract: The fission yeast Sty1/Spc1 mitogen-activated protein (MAP) kinase is a member of the eukaryotic stress-activated MAP kinase (SAPK) family. We have identified a protein, Sin1, that interacts with Sty1/Spc1 which is a member of a new evolutionarily conserved gene family. Cells lacking Sin1 display many, but not all, of the phenotypes of cells lacking the Sty1/Spc1 MAP kinase including sterility, multiple stress sensitivity and a cell-cycle delay. Sin1 is phosphorylated after stress but this is not Sty1/Spc1-dependent. Importantly, Sin1 is not required for activation of Sty1/Spc1 but is required for stress-dependent transcription via its substrate, Atf1. We find that in the absence of Sin1, Sty1/Spc1 appears to translocate to the nucleus but Atf1 is not fully phosphorylated and becomes unstable in response to environmental stress. Sin1 is also required for effective transcription via the AP-1 factor Pap1 but does not prevent its nuclear translocation. Remarkably chimaeric fusions of sin1 with chicken sin1 sequences rescue loss of sin1 function. We conclude that Sin1 is a novel component of the eukaryotic SAPK pathway.
authors.affiliation: Division of Yeast Genetics, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
authors.forename: M G
authors.initials: MG
authors.lastname: Wilkinson
authors.forename: T S
authors.initials: TS
authors.lastname: Pino
authors.forename: S
authors.initials: S
authors.lastname: Tournier
authors.forename: V
authors.initials: V
authors.lastname: Buck
authors.forename: H
authors.initials: H
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Christiansen
authors.forename: D G
authors.initials: DG
authors.lastname: Wilkinson
authors.forename: J B
authors.initials: JB
authors.lastname: Millar
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D051697:Activating Transcription Factor 1; D000595:Amino Acid Sequence; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D019143:Evolution, Molecular; D005656:Fungal Proteins; D020928:Mitogen-Activated Protein Kinases; D008969:Molecular Sequence Data; D005810:Multigene Family; D018384:Oxidative Stress; D000073718:Pancreatitis-Associated Proteins; D010750:Phosphoproteins; D010766:Phosphorylation; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: D051697:Activating Transcription Factor 1; D050976:Basic-Leucine Zipper Transcription Factors; D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; D017931:DNA Primers; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D000073718:Pancreatitis-Associated Proteins; C105096:Pap1 protein, S pombe; D010750:Phosphoproteins; C000612141:REG3A protein, human; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C000602849:Sin1 protein, S pombe; C106740:atf1 protein, S pombe; C069938:SPT2 protein, S cerevisiae; D000123:Acetyltransferases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C095409:sty1 protein, S pombe