Mcs4 mitotic catastrophe suppressor regulates the fission yeast cell cycle through the Wik1-Wis1-Spc1 kinase cascade.
Spc1 in Schizosaccharomyces pombe is a member of the stress-activated protein kinase family, an evolutionary conserved subfamily of mitogen-activated protein kinases (MAPKs). Spc1 is activated by a MAPK kinase homologue, Wis1, and negatively regulated by Pyp1 and Pyp2 tyrosine phosphatases. Mutations in the spc1+ and wis1+ genes cause a G2 ... cell cycle delay that is exacerbated during stress. Herein, we describe two upstream regulators of the Wis1-Spc1 cascade. wik1+ (Wis1 kinase) was identified from its homology to budding yeast SSK2, which encodes a MAPKK kinase that regulates the HOG1 osmosensing pathway. Delta wik1 cells are impaired in stress-induced activation of Spc1 and show a G2 cell cycle delay and osmosensitive growth. Moreover, overproduction of a constitutively active form of Wik1 induces hyperactivation of Spc1 in wis1(+)-dependent manner, suggesting that Wik1 regulates Spc1 through activation of Wis1. A mutation of mcs4+ (mitotic catastrophe suppressor) was originally isolated as a suppressor of the mitotic catastrophe phenotype of a cdc2-3w wee1-50 double mutant. We have found that mcs4- cells are defective at activation of Spc1 in response to various forms of stress. Epistasis analysis has placed Mcs4-upstream of Wik1 in the Spc1 activation cascade. These results indicate that Mcs4 is part of a sensor system for multiple environmental signals that modulates the timing of entry into mitosis by regulating the Wik1-Wis1-Spc1 kinase cascade. Inactivation of the sensor system delays the onset of mitosis and rescues lethal premature mitosis in cdc2-3w wee1-50 cells.
Mesh Terms:
Amino Acid Sequence, Calcium-Calmodulin-Dependent Protein Kinases, Cell Cycle, Cell Cycle Proteins, Fungal Proteins, G2 Phase, Gene Deletion, Gene Expression Regulation, Genes, Suppressor, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Mutation, Protein-Serine-Threonine Kinases, Saccharomyces cerevisiae, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Signal Transduction
Amino Acid Sequence, Calcium-Calmodulin-Dependent Protein Kinases, Cell Cycle, Cell Cycle Proteins, Fungal Proteins, G2 Phase, Gene Deletion, Gene Expression Regulation, Genes, Suppressor, Mitogen-Activated Protein Kinase Kinases, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Mutation, Protein-Serine-Threonine Kinases, Saccharomyces cerevisiae, Schizosaccharomyces, Schizosaccharomyces pombe Proteins, Signal Transduction
Mol. Biol. Cell
Date: Mar. 01, 1997
PubMed ID: 9188094
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