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
Summary
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.
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