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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

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PP1 promotes cyclin B destruction and the metaphase-anaphase transition by dephosphorylating CDC20

James Bancroft1, James Holder2, Zoë Geraghty1

  • 1Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK.

Molecular Biology of the Cell
|August 7, 2020
PubMed

Insights

Protein phosphatase 1 (PP1) promotes cyclin B destruction, enabling cell division. This phosphatase removes inhibitory phosphorylation on CDC20, facilitating the metaphase-to-anaphase transition in human cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Sister chromatid segregation and anaphase initiation depend on ubiquitin-dependent proteolysis of cyclin B and securin.
  • The anaphase-promoting complex/cyclosome coactivator CDC20 (APC/CCDC20) is the primary ubiquitin E3 ligase for these proteins.
  • APC/CCDC20 activity is tightly regulated by CDK1-cyclin B and opposing phosphatases (PP1, PP2A) through phosphorylation.

Purpose of the Study:

  • To investigate the role of PP1 in regulating APC/CCDC20 activity and the metaphase-to-anaphase transition.
  • To determine how PP1 influences CDC20 phosphorylation and subsequent cyclin B degradation.

Main Methods:

  • Depletion and chemical inhibition of PP1 in human cells.
  • Analysis of cyclin B stability and metaphase-to-anaphase transition timing.
  • Utilizing CDC20 phosphorylation-defective mutants (CDC206A) to assess PP1 dependency.

Main Results:

  • PP1 promotes cyclin B destruction at anaphase onset by removing inhibitory N-terminal phosphorylation on CDC20.
  • PP1 depletion or inhibition delays the metaphase-to-anaphase transition due to cyclin B stabilization.
  • Cells expressing CDC206A mutants bypass the requirement for PP1, indicating CDK1 phosphorylation sites on CDC20 are critical for PP1's function.

Conclusions:

  • PP1 is essential for timely cyclin B degradation and progression through mitosis.
  • PP1 facilitates the metaphase-to-anaphase transition by enhancing APC/CCDC20-mediated cyclin B destruction in human cells.

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