Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex

J D Reimann1, E Freed, J Y Hsu

  • 1Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.

Cell
|June 8, 2001
PubMed

Insights

We discovered Emi1, an early mitotic inhibitor that prevents premature anaphase promoting complex/cyclosome (APC) activation. This regulation is crucial for timely cell cycle progression during mitosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitosis is a critical cell division process regulated by complex molecular machinery.
  • The anaphase promoting complex/cyclosome (APC) is a key E3 ubiquitin ligase that controls cell cycle progression.
  • Dysregulation of mitotic progression can lead to severe cellular defects and diseases.

Purpose of the Study:

  • To identify and characterize novel regulators of early mitosis.
  • To elucidate the mechanism by which Emi1 controls APC activity.
  • To understand the role of Emi1 in cell cycle progression.

Main Methods:

  • Xenopus egg extracts were used to study cell cycle regulation.
  • Immunodepletion and expression of non-degradable Emi1 were employed.
  • Co-immunoprecipitation assays were performed to study protein interactions.

Main Results:

  • Emi1, an F-box protein, inhibits APC activity through its zinc-binding domain.
  • Emi1 accumulates before mitosis and is degraded during mitosis independently of APC.
  • Emi1 depletion delays mitotic entry, while non-degradable Emi1 causes a mitotic block by stabilizing APC substrates.
  • Emi1 interacts with Cdc20, an APC activator, and Cdc20 can override Emi1-induced inhibition of cyclin B destruction.

Conclusions:

  • Emi1 acts as an early mitotic inhibitor by preventing premature APC activation.
  • Emi1 is a critical regulator of the timing of mitotic progression.
  • Emi1 function provides insight into the delay between cyclin B/Cdc2 activation and cyclin B destruction in mitosis.

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