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A role for Hsp90 in cell cycle control: Wee1 tyrosine kinase activity requires interaction with Hsp90
R Aligue1, H Akhavan-Niak, P Russell
1Department of Molecular Biology, Scripps Research Institute, La Jolla, CA 92037.
Abstract:
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.
Insights
The Hsp90 chaperone protein Swo1 is essential for the activity of Wee1 kinase, which controls cell cycle progression. This discovery reveals a novel role for Hsp90 in regulating the cell cycle.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Wee1 protein kinase regulates the G2 phase length via inhibitory phosphorylation of Cdc2-cyclin B.
- Cell cycle arrest can be caused by the overproduction of Wee1 kinase.
Purpose of the Study:
- To investigate the genetic interactions between Wee1 and suppressors of Wee1 overproduction.
- To elucidate the molecular function of the suppressor of wee1 overproduction 1 (swo1) gene.
Main Methods:
- Isolation and characterization of suppressor of wee1 overproduction (swo) mutations.
- Genetic analysis in a wee1+ background.
- Coimmunoprecipitation assays to detect protein interactions.
- Phenotypic analysis of mutant strains at different temperatures.
Main Results:
- A class of mutations, swo1, suppressed Wee1 overproduction-induced G2 arrest and caused temperature-sensitive lethality.
- The swo1+ gene encodes a member of the Hsp90 family of chaperone proteins.
- Swo1 coimmunoprecipitated with Wee1, indicating a physical interaction.
- The swo1-26 mutant exhibited premature mitosis at semi-permissive temperatures.
Conclusions:
- The Hsp90 chaperone Swo1 is required for the formation of active Wee1 tyrosine kinase.
- This interaction is crucial for proper cell cycle control, specifically regulating the G2/M transition.
- Hsp90 plays an unexpected but vital role in cell cycle regulation through its interaction with Wee1.