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The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation
R Visintin1, K Craig, E S Hwang
1Whitehead Institute for Biomedical Research, Cambridge Center, Massachusetts 02142, USA.
Abstract:
Exit from mitosis requires the inactivation of mitotic cyclin-dependent kinases (CDKs) by an unknown mechanism. We show that the Cdc14 phosphatase triggers mitotic exit by three parallel mechanisms, each of which inhibits Cdk activity. Cdc14 dephosphorylates Sic1, a Cdk inhibitor, and Swi5, a transcription factor for SIC1, and induces degradation of mitotic cyclins, likely by dephosphorylating the activator of mitotic cyclin degradation, Cdh1/Hct1. Feedback between these pathways may lead to precipitous collapse of mitotic CDK activity and help coordinate exit from mitosis.
Insights
The Cdc14 phosphatase triggers mitotic exit by inactivating mitotic cyclin-dependent kinases (CDKs) through three parallel pathways. This coordinated action ensures the timely and precise collapse of CDK activity, facilitating cell cycle progression.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Mitotic exit, crucial for cell division, necessitates the inactivation of mitotic cyclin-dependent kinases (CDKs).
- The precise molecular mechanisms governing mitotic CDK inactivation remain incompletely understood.
Purpose of the Study:
- To elucidate the role of the Cdc14 phosphatase in triggering mitotic exit.
- To identify the specific mechanisms by which Cdc14 inhibits CDK activity.
Main Methods:
- Investigated the function of Cdc14 phosphatase in regulating mitotic CDK activity.
- Analyzed the dephosphorylation of key substrates including Sic1, Swi5, and Cdh1/Hct1.
Main Results:
- Demonstrated that Cdc14 triggers mitotic exit via three parallel pathways that inhibit CDK activity.
- Showed Cdc14 dephosphorylates Sic1 (a CDK inhibitor) and Swi5 (a transcription factor for SIC1).
- Indicated Cdc14 induces mitotic cyclin degradation, likely by dephosphorylating Cdh1/Hct1 (activator of cyclin degradation).
Conclusions:
- Cdc14 phosphatase is a central regulator of mitotic exit, acting through multiple coordinated mechanisms.
- Feedback loops between these pathways likely ensure a rapid and complete inactivation of mitotic CDK activity.
- This coordinated regulation is essential for the precise timing of cell cycle progression out of mitosis.