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Related Experiment Videos

Protein phosphatases and cell division cycle control.

M Yanagida1, N Kinoshita, E M Stone

  • 1Department of Biophysics, Faculty of Science, Kyoto University, Japan.

Ciba Foundation Symposium
|January 1, 1992
PubMed
Summary

Fission yeast protein phosphatases PP1 and PP2A regulate entry into mitosis. Loss of these phosphatases causes premature mitosis, while their overexpression delays it, highlighting their crucial cell cycle control roles.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • Fission yeast possesses multiple protein phosphatase genes involved in cell cycle control.
  • Functional overlap necessitates multiple genetic alterations to observe clear phenotypes.
  • Protein phosphatases PP1 and PP2A play critical roles in regulating mitotic entry and progression.

Purpose of the Study:

  • To investigate the roles of protein phosphatase 1 (PP1)-like dis2/sds21 and PP2A-like ppa2 in fission yeast cell cycle control.
  • To elucidate the mechanisms by which these phosphatases regulate entry into and progression through mitosis.
  • To identify novel regulators of phosphatase activity in mitosis.

Main Methods:

  • Genetic analysis of fission yeast mutants lacking specific protein phosphatase activities (dis2/sds21, ppa2).
  • Phenotypic analysis including cell cycle progression, H1 kinase activity, and sister chromatid disjunction.
  • Investigating the effects of hydroxyurea and okadaic acid on mutant phenotypes.
  • Examining genetic interactions with known mitotic regulators.
  • Characterizing the interaction between dis2 phosphatase and its novel regulator Sds22+.

Main Results:

  • Loss of PP1-like dis2/sds21 or PP2A-like ppa2 activity leads to premature entry into mitosis.
  • PP1/PP2A phosphatases negatively regulate entry into mitosis, potentially by inhibiting p34cdc2/cyclin kinase.
  • Disruption of PP1-like activity prevents inactivation of the p34cdc2/cyclin complex post-mitotic entry.
  • Overexpression of PP1-like phosphatases delays mitotic entry.
  • A novel regulator, Sds22+, binds dis2 phosphatase and is essential for metaphase-anaphase progression.

Conclusions:

  • Both PP1- and PP2A-like phosphatases are essential negative regulators of mitotic entry in fission yeast.
  • Dis2/sds21 and ppa2/ppa1 phosphatases have distinct roles in mitotic progression, particularly in the inactivation of the p34cdc2/cyclin complex.
  • The Sds22+ protein is a novel regulator that modulates dis2 phosphatase activity and substrate specificity, crucial for anaphase.
  • These findings deepen the understanding of cell cycle control mechanisms mediated by protein phosphatases.

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