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Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins

J D Reimann1, B E Gardner, F Margottin-Goguet

  • 1Department of Pathology, Stanford University School of Medicine, Stanford, California 94305-5324, USA.

Genes & Development
|December 26, 2001
PubMed

Insights

Early mitotic inhibitor Emi1 binds and inhibits both APC(Cdh1) and APC(Cdc20) ubiquitin ligases, unlike Mad2 proteins. Emi1 requires zinc and prevents substrate binding, revealing a novel inhibition mechanism.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • The anaphase-promoting complex/cyclosome (APC) is a crucial ubiquitin ligase regulating cell cycle progression.
  • APC activity is tightly controlled by various activators and inhibitors, including Cdc20, Cdh1, Mad2, Mad2B, and Emi1.

Purpose of the Study:

  • To elucidate the mechanism by which early mitotic inhibitor Emi1 inhibits the APC.
  • To compare the inhibitory mechanisms of Emi1 with those of Mad2 proteins.

Main Methods:

  • Investigated the binding interactions of Emi1 with APC(Cdh1) and APC(Cdc20).
  • Assessed the effect of Emi1 on substrate binding to the APC.
  • Determined the requirement of zinc for Emi1's inhibitory activity.
  • Examined the impact of Emi1 on cyclin A stability in embryonic cells.

Main Results:

  • Emi1 inhibits both APC(Cdh1) and APC(Cdc20), unlike Mad2 proteins which show preferential inhibition.
  • Emi1 requires zinc for its APC inhibitory activity.
  • Emi1 binds to the substrate-binding region of Cdc20, preventing substrate recruitment to the APC.
  • Emi1 stabilizes cyclin A in embryonic cells.

Conclusions:

  • Emi1 employs a novel mechanism to inhibit the APC by directly blocking substrate binding.
  • Emi1's inhibitory activity is dependent on zinc, distinguishing it from Mad2-mediated inhibition.
  • Understanding Emi1's mechanism provides insights into cell cycle regulation and potential therapeutic targets.

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