A WD repeat protein controls the cell cycle and differentiation by negatively regulating Cdc2/B-type cyclin complexes.
In the fission yeast Schizosaccharomyces pombe, p34(cdc2) plays a central role controlling the cell cycle. We recently isolated a new gene named srw1(+), capable of encoding a WD repeat protein, as a multicopy suppressor of hyperactivated p34(cdc2). Cells lacking srw1(+) are sterile and defective in cell cycle controls. When starved for nitrogen source, they fail to effectively arrest in G1 and die of accelerated mitotic catastrophe if regulation of p34(cdc2)/Cdc13 by inhibitory tyrosine phosphorylation is compromised by partial inactivation of Wee1 kinase. Fertility is restored to the disruptant by deletion of Cig2 B-type cyclin or slight inactivation of p34(cdc2). srw1(+) shares functional similarity with rum1(+), having abilities to induce endoreplication and restore fertility to rum1 disruptants. In the srw1 disruptant, Cdc13 fails to be degraded when cells are starved for nitrogen. We conclude that Srw1 controls differentiation and cell cycling at least by negatively regulating Cig2- and Cdc13-associated p34(cdc2) and that one of its roles is to down-regulate the level of the mitotic cyclin particularly in nitrogen-poor environments.
Yamaguchi
S
S
Department of Biochemistry, Faculty of Medicine, The University of Tokyo, Hongo, Tokyo 113, Japan.
Murakami
H
H
Okayama
H
H
D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D003001:Cloning, Molecular; D019926:Cyclin B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016213:Cyclins / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D005298:Fertility / Q000235:genetics; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal / Q000235:genetics / Q000502:physiology; D005804:Genes, Lethal / Q000235:genetics; D016153:Genes, Suppressor / Q000235:genetics; D008938:Mitosis; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009584:Nitrogen / Q000378:metabolism; D009687:Nuclear Proteins; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D012568:Schizosaccharomyces / Q000166:cytology* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins
D018797:Cell Cycle Proteins; C080328:Cig2 protein, S pombe; D019926:Cyclin B; D016213:Cyclins; D005656:Fungal Proteins; D009687:Nuclear Proteins; C086077:Rum1 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; C113000:srw1 protein, S pombe; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases; D016203:CDC2 Protein Kinase; D009584:Nitrogen