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APC/C(Cdc20) targets E2F1 for degradation in prometaphase

Melissa J Peart1, Masha V Poyurovsky, Elizabeth M Kass

  • 1Department of Biological Sciences, Columbia University, New York, NY, USA.

Cell Cycle (Georgetown, Tex.)
|October 16, 2010
PubMed

Insights

The anaphase promoting complex or cyclosome (APC/C) targets E2F1 for degradation during mitosis. APC/C(Cdc20) regulates E2F1 stability, controlling its levels and impacting cell homeostasis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • E2F1 activity is tightly regulated, with previous work highlighting Chk1 and Chk2 in its stabilization.
  • Understanding E2F1 protein turnover is crucial for comprehending its role in cell cycle control.

Purpose of the Study:

  • To investigate the mechanisms governing E2F1 protein turnover.
  • To identify the role of the anaphase promoting complex or cyclosome (APC/C) in regulating E2F1 stability.

Main Methods:

  • Investigated E2F1 as a substrate of the APC/C ubiquitin ligase.
  • Examined the effect of APC/C activators (Cdh1, Cdc20) on E2F1 levels.
  • Utilized co-expression of E2F1/DP1 and Cdc20 knockdown/siRNA experiments.
  • Performed cell synchronization studies.

Main Results:

  • E2F1 was identified as a substrate of the APC/C.
  • Ectopic expression of Cdh1 and Cdc20 decreased E2F1 protein levels.
  • The E2F1/DP1 heterodimer was protected from APC/C-mediated degradation.
  • Cdc20 knockdown led to increased and stable E2F1 levels.
  • siRNA against Cdc20 caused E2F1 accumulation in prometaphase cells.

Conclusions:

  • APC/C(Cdc20) targets E2F1 for degradation during early mitosis.
  • This reveals a novel mechanism for controlling free E2F1 levels.
  • Dysregulation of this process may affect cell survival and homeostasis.

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