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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Create, activate, destroy, repeat: Cdk1 controls proliferation by limiting transcription factor activity.

Jennifer A Benanti1

  • 1Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, 01605, USA. jennifer.benanti@umassmed.edu.

Current Genetics
|November 23, 2015
PubMed
Summary

Environmental stress impacts cell cycle progression by altering the phosphorylation of the Hcm1 transcription factor. The phosphatase calcineurin deactivates Hcm1, slowing cell proliferation during unfavorable conditions.

Keywords:
CalcineurinCell cycleCyclin-dependent kinaseGene expressionHcm1

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Area of Science:

  • Cell biology
  • Molecular biology
  • Biochemistry

Background:

  • Cell cycle progression relies on transcription factors coordinating gene expression.
  • Hcm1 is a key forkhead protein regulating S-phase genes in budding yeast.
  • Cyclin-dependent kinase 1 (Cdk1) regulates Hcm1 activity through phosphorylation, controlling activation and degradation.

Purpose of the Study:

  • To elucidate the mechanisms controlling the differential phosphorylation timing of Hcm1.
  • To investigate the role of phosphatases in regulating Hcm1 activity in response to environmental stress.
  • To understand how Hcm1 regulation impacts cell proliferation under stress conditions.

Main Methods:

  • Investigated the role of the phosphatase calcineurin in Hcm1 regulation.
  • Analyzed the effect of environmental stress on Hcm1 phosphorylation.
  • Studied the impact of calcineurin-mediated dephosphorylation on Hcm1 activity and cell proliferation.

Main Results:

  • Calcineurin specifically removes activating phosphates from Hcm1 under environmental stress.
  • This dephosphorylation by calcineurin leads to the inactivation of Hcm1.
  • Inactivation of Hcm1 results in the slowing of cellular proliferation during unfavorable growth conditions.

Conclusions:

  • A phosphatase (calcineurin) actively modifies phosphosite distribution on a cell cycle transcription factor (Hcm1) to control proliferation.
  • This regulatory mechanism adds complexity to cell cycle control networks.
  • This phosphoregulation paradigm is likely conserved across diverse biological systems for cell cycle control.