title: Phosphorylation of Mei2 and Ste11 by Pat1 kinase inhibits sexual differentiation via ubiquitin proteolysis and 14-3-3 protein in fission yeast.
abstract: Fission yeast Pat1 kinase inhibits sexual differentiation by phosphorylating the meiotic inducer Mei2 and the transcription factor Ste11. Here, we show how Pat1 downregulates these proteins. Mei2 is degraded via a ubiquitin-proteasome pathway in a phosphorylation-dependent fashion. The E2 Ubc2 and the E3 Ubr1 are required for this proteolysis. In addition, Pat1 negatively regulates Ste11 via Rad24/14-3-3, thereby repressing mei2+ transcription. The Pat1 phosphorylation sites of Ste11 match the consensus recognition sequence for 14-3-3. Rad24 binds preferentially to phosphorylated Ste11, and this binding results in inhibition of the transcriptional activation capacity of Ste11. Overall, therefore, these results show that Pat1 coordinates concerted molecular mechanisms that govern the sexual differentiation developmental decision.
authors.affiliation: Laboratory of Cell Regulation, Imperial Cancer Research Fund, United Kingdom. toda@icrf.icnet.uk
authors.forename: K
authors.initials: K
authors.lastname: Kitamura
authors.forename: S
authors.initials: S
authors.lastname: Katayama
authors.forename: S
authors.initials: S
authors.lastname: Dhut
authors.forename: M
authors.initials: M
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Watanabe
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Toda
mesh_terms: D048948:14-3-3 Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D017930:Genes, Reporter / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D008025:Ligases / Q000235:genetics / Q000378:metabolism; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis / Q000502:physiology; D009097:Multienzyme Complexes / Q000378:metabolism; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes; D044767:Ubiquitin-Protein Ligases
chemical_list: D048948:14-3-3 Proteins; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009097:Multienzyme Complexes; D016601:RNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; D025801:Ubiquitin; C088896:mei2 protein, S pombe; C501114:rad24 protein, S pombe; D014446:Tyrosine 3-Monooxygenase; D044763:Ubiquitin-Conjugating Enzymes; C066066:UBR1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D011494:Protein Kinases; C087019:ran1 protein, S pombe; D017346:Protein Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases; C067018:Ste11 protein, S cerevisiae; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D008025:Ligases