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Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell cycle

N Watanabe1, M Broome, T Hunter

  • 1Molecular Biology and Virology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

The EMBO Journal
|May 1, 1995
PubMed

Insights

Human WEE1Hu, a Mik1-related kinase, regulates cell division by phosphorylating cyclin-dependent kinases (CDKs) on Y15. Its activity is controlled by phosphorylation and degradation, inhibiting mitosis before M phase.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cyclin-dependent kinases (CDKs) are crucial cell cycle regulators.
  • Negative regulation of CDKs occurs via phosphorylation at T14 and Y15 residues.
  • Wee1 and Mik1 are known kinases that phosphorylate Y15 in fission yeast.

Purpose of the Study:

  • To investigate the endogenous WEE1Hu protein in human cells.
  • To determine the relationship between WEE1Hu and known Wee1/Mik1 kinases.
  • To elucidate the regulatory mechanisms and cell cycle role of WEE1Hu.

Main Methods:

  • Analysis of endogenous WEE1Hu protein products in human cells.
  • Immunoprecipitation and in vitro kinase assays.
  • Assessment of WEE1Hu protein levels and activity throughout the cell cycle.

Main Results:

  • The original WEE1Hu cDNA was N-terminally truncated; the full-length protein shows similarity to Mik1.
  • Endogenous WEE1Hu phosphorylates cyclin-associated CDKs on Y15.
  • WEE1Hu activity and protein levels peak in S/G2, decrease in M phase due to hyperphosphorylation and degradation.

Conclusions:

  • WEE1Hu is a Mik1-related protein, not a direct Wee1 homologue.
  • WEE1Hu activity is regulated by phosphorylation and proteolysis.
  • WEE1Hu functions in inhibiting mitosis by phosphorylating cyclin B1-Cdc2 before M phase.

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