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Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
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Nuclear PP2A-Cdc55 prevents APC-Cdc20 activation during the spindle assembly checkpoint

Valentina Rossio1, Takeshi Michimoto, Takeshi Sasaki

  • 1Department of Biology and Rosenstiel Basic Biomedical Sciences Research Center, Brandeis University, 415 South Street, Waltham, MA 02454, USA.

Journal of Cell Science
|July 27, 2013
PubMed

Insights

Nuclear PP2A-Cdc55 dephosphorylates and inactivates the anaphase-promoting complex (APC) to maintain the spindle assembly checkpoint (SAC) during spindle damage. Spatial control of Cdc55 by Zds1 proteins is crucial for SAC regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cdc55 is a regulatory subunit of protein phosphatase 2A (PP2A).
  • PP2A-Cdc55 is essential for the spindle assembly checkpoint (SAC) in budding yeast.
  • The precise regulation and molecular targets of PP2A-Cdc55 in the SAC remain unclear.

Purpose of the Study:

  • To identify molecular targets of PP2A-Cdc55 during the SAC.
  • To investigate the role of nuclear localization of Cdc55 in SAC function.
  • To elucidate the regulatory mechanisms controlling PP2A-Cdc55 activity.

Main Methods:

  • Isolation and characterization of novel Cdc55 mutants defective in SAC.
  • Manipulation of Cdc55 nucleocytoplasmic distribution.
  • Analysis of anaphase-promoting complex (APC) activity.
  • Investigation of Cdc55-binding proteins Zds1 and Zds2.

Main Results:

  • PP2A-Cdc55 dephosphorylates and inactivates the anaphase-promoting complex (APC)-Cdc20 complex upon spindle damage.
  • Nuclear localization of Cdc55 is essential for SAC activity.
  • Zds1 and Zds2 proteins inhibit nuclear accumulation of Cdc55 and SAC activity.

Conclusions:

  • Nuclear PP2A-Cdc55 directly regulates APC-Cdc20 to ensure SAC fidelity.
  • Spatial control of PP2A-Cdc55 by Zds1 family proteins is critical for precise regulation of the SAC and mitotic progression.
Keywords:
APCAnaphase-promoting complexCdc55PP2AProtein phosphatase 2ASACSpindle assembly checkpointZds1

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