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The Zds proteins control entry into mitosis and target protein phosphatase 2A to the Cdc25 phosphatase

Sidonie Wicky1, Hendri Tjandra, David Schieltz

  • 1Department of Molecular, Cell, and Developmental Biology, Univ. of California, Santa Cruz, CA 95064, USA.

Molecular Biology of the Cell
|December 2, 2010
PubMed

Insights

The Zds proteins regulate protein phosphatase 2A (PP2A) by targeting it to Cdc25, a key enzyme controlling entry into mitosis. This discovery clarifies PP2A

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Entry into mitosis is a critical cell cycle event regulated by opposing kinases (Wee1) and phosphatases (Cdc25).
  • Protein phosphatase 2A (PP2A) is known to regulate both Wee1 and Cdc25, but its specific role in mitotic entry remains unclear.
  • In budding yeast, PP2A associated with the Cdc55 regulatory subunit (PP2A(Cdc55)) is implicated in controlling mitotic entry.

Purpose of the Study:

  • To elucidate the function and regulation of PP2A(Cdc55) in the control of mitotic entry.
  • To identify proteins that specifically target PP2A(Cdc55) activity.
  • To understand the role of Zds proteins in the regulation of cell cycle progression.

Main Methods:

  • Biochemical analysis to determine complex formation between Zds proteins and PP2A(Cdc55).
  • Functional assays using conditional inactivation of Zds proteins to assess their role in mitosis.
  • Phosphorylation analysis of Zds1 during the cell cycle.

Main Results:

  • Zds1 and Zds2 form a stable stoichiometric complex with PP2A(Cdc55).
  • The Zds-PP2A(Cdc55) complex specifically targets Cdc25 for dephosphorylation, not Wee1.
  • Zds proteins are essential for mitotic entry, and Zds1 phosphorylation is cell cycle-dependent.

Conclusions:

  • Zds proteins are crucial regulators that direct PP2A(Cdc55) activity towards Cdc25.
  • This interaction plays a vital role in controlling entry into mitosis.
  • Upstream signaling pathways regulating PP2A(Cdc55) activity are important for cell cycle control.

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