title: The role of the RACK1 ortholog Cpc2p in modulating pheromone-induced cell cycle arrest in fission yeast.
abstract: The detection and amplification of extracellular signals requires the involvement of multiple protein components. In mammalian cells the receptor of activated C kinase (RACK1) is an important scaffolding protein for signal transduction networks. Further, it also performs a critical function in regulating the cell cycle by modulating the G1/S transition. Many eukaryotic cells express RACK1 orthologs, with one example being Cpc2p in the fission yeast Schizosaccharomyces pombe. In contrast to RACK1, Cpc2p has been described to positively regulate, at the ribosomal level, cells entry into M phase. In addition, Cpc2p controls the stress response pathways through an interaction with Msa2p, and sexual development by modulating Ran1p/Pat1p. Here we describe investigations into the role, which Cpc2p performs in controlling the G protein-mediated mating response pathway. Despite structural similarity to Gβ-like subunits, Cpc2p appears not to function at the G protein level. However, upon pheromone stimulation, cells overexpressing Cpc2p display substantial cell morphology defects, disorientation of septum formation and a significantly protracted G1 arrest. Cpc2p has the potential to function at multiple positions within the pheromone response pathway. We provide a mechanistic interpretation of this novel data by linking Cpc2p function, during the mating response, with its previous described interactions with Ran1p/Pat1p. We suggest that overexpressing Cpc2p prolongs the stimulated state of pheromone-induced cells by increasing ste11 gene expression. These data indicate that Cpc2p regulates the pheromone-induced cell cycle arrest in fission yeast by delaying cells entry into S phase.
authors.affiliation: Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry, United Kingdom. m.mos@warwick.ac.uk
authors.forename: Magdalena
authors.initials: M
authors.lastname: Mos
authors.forename: Manuel A
authors.initials: MA
authors.lastname: Esparza-Franco
authors.forename: Emma L
authors.initials: EL
authors.lastname: Godfrey
authors.forename: Kathryn
authors.initials: K
authors.lastname: Richardson
authors.forename: John
authors.initials: J
authors.lastname: Davey
authors.forename: Graham
authors.initials: G
authors.lastname: Ladds
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D044387:GTP-Binding Protein beta Subunits / Q000737:chemistry / Q000378:metabolism; D015870:Gene Expression; D008958:Models, Molecular; D010675:Pheromones / Q000494:pharmacology*; D011487:Protein Conformation; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D044387:GTP-Binding Protein beta Subunits; D010675:Pheromones; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D029702:Schizosaccharomyces pombe Proteins