A role for Hsp90 in cell cycle control: Wee1 tyrosine kinase activity requires interaction with Hsp90.
Wee1 protein kinase regulates the length of G2 phase by carrying out the inhibitory tyrosyl phosphorylation of Cdc2-cyclin B kinase. Mutations were isolated that suppressed the G2 cell cycle arrest caused by overproduction of Wee1. One class of swo (suppressor of wee1 overproduction) mutation, exemplified by swo1-26, also caused a temperature sensitive lethal phenotype in a wee1+ background. The swo1+ gene encodes a member of the Hsp90 family of stress proteins. Swo1 is essential for viability at all temperatures. Swo1 coimmunoprecipitates with Wee1, showing that the two proteins interact. The swo1-26 mutant undergoes premature mitosis when grown at a semi-permissive temperature. These data strongly indicate that formation of active Wee1 tyrosine kinase requires interaction with Swo1, perhaps in a manner analogous to the previously demonstrated interaction between Hsp90 and v-src tyrosine kinase. These observations demonstrate a unexpected role for Hsp90 in cell cycle control.
Aligue
R
R
Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
Akhavan-Niak
H
H
Russell
P
P
D000595:Amino Acid Sequence; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins; D004795:Enzyme Stability; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics; D005804:Genes, Lethal / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006358:Hot Temperature; D008938:Mitosis; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D012568:Schizosaccharomyces / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D013489:Suppression, Genetic
D018797:Cell Cycle Proteins; D018841:HSP90 Heat-Shock Proteins; D009687:Nuclear Proteins; D029702:Schizosaccharomyces pombe Proteins; C091275:Swo1 protein, S pombe; C068689:wee1 protein, S pombe; D011505:Protein-Tyrosine Kinases