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Cdc14 activates cdc15 to promote mitotic exit in budding yeast
1Department of Physiology, University of California, San Francisco, CA 94143-0444, USA.
Current Biology : CB
|June 6, 2000
Summary
Mitotic cyclin-dependent kinases (Cdks) inactivation is crucial for cell cycle progression. In budding yeast, Cdc15 protein kinase activity is inhibited by phosphorylation, and dephosphorylation by Cdc14 promotes mitotic exit.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cellular division requires the precise regulation of cyclin-dependent kinases (Cdks).
- In budding yeast (Saccharomyces cerevisiae), the phosphatase Cdc14 plays a critical role in Cdk inactivation, triggering mitotic exit.
- Cdc14 activation is orchestrated by a complex regulatory network, including the protein kinase Cdc15.
Purpose of the Study:
- To investigate the regulatory role of phosphorylation on the protein kinase Cdc15.
- To elucidate the relationship between Cdc15 and the phosphatase Cdc14 in mitotic exit control.
Main Methods:
- In vivo and in vitro phosphorylation assays.
- Analysis of non-phosphorylatable Cdc15 mutants.
- Observation of Cdc15 dephosphorylation upon Cdc14 overproduction.
Main Results:
- Cdc15 is phosphorylated at multiple Cdk-consensus sites during the cell cycle and transiently dephosphorylated in late mitosis.
- Phosphorylation inhibits Cdc15 function in promoting mitotic exit, as evidenced by a hyperactive non-phosphorylatable mutant.
- Cdc14 directly dephosphorylates inhibitory phosphates on Cdc15 in vitro and in vivo.
Conclusions:
- Cdc15 acts as both an activator and a substrate of Cdc14, highlighting a novel regulatory feedback loop.
- While positive feedback on Cdc14 activation is possible, it is not essential for its function.
- Cdc15 dephosphorylation by Cdc14 may facilitate additional, independent functions in mitotic exit.