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Fission yeast Clp1p phosphatase affects G2/M transition and mitotic exit through Cdc25p inactivation

Benjamin A Wolfe1, Kathleen L Gould

  • 1Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.

The EMBO Journal
|February 7, 2004
PubMed

Insights

The Cdc14 phosphatase Clp1p inactivates the Cdc25 protein at mitotic exit in fission yeast. This ensures proper cell cycle progression and prevents premature entry into the next mitosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The Cdc14 family of phosphatases reverses proline-directed phosphorylation events crucial for cell cycle regulation.
  • In Saccharomyces cerevisiae, Cdc14p inactivates Cdk1p at mitotic exit by reversing Cdk1p-dependent phosphorylations.
  • Cdk1p activity is essential for mitotic entry in eukaryotes and regulates itself by activating Cdc25p and inhibiting Wee1p.

Purpose of the Study:

  • To investigate the role of Schizosaccharomyces pombe Clp1p, a Cdc14p homolog, in disrupting the Cdk1p auto-amplification loop.
  • To determine if Clp1p is involved in the inactivation of Cdc25p at the end of mitosis.

Main Methods:

  • Investigated the function of Clp1p in fission yeast.
  • Analyzed the dephosphorylation, destabilization, and inactivation of Cdc25p by Clp1p.
  • Examined the interaction between Clp1p, Cdc25p, and the anaphase-promoting complex/cyclosome (APC/C).

Main Results:

  • Clp1p is essential for dephosphorylating, destabilizing, and inactivating Cdc25p at the end of mitosis.
  • Clp1p facilitates the recognition of Cdc25p by the APC/C, an E3 ubiquitin ligase.
  • Failure to inactivate Cdc25p leads to delayed anaphase progression, impaired septation initiation network signaling, and advanced entry into the next cell cycle.

Conclusions:

  • Clp1p plays a critical role in the timely inactivation and degradation of Cdc25p, ensuring proper mitotic exit.
  • This mechanism highlights a conserved role for Cdc14 phosphatases in Cdk1p inactivation across eukaryotes.
  • Dysregulation of Cdc25p inactivation by Clp1p has significant consequences for cell cycle progression and fidelity.

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