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RCS1, a substrate of APC/C, controls the metaphase to anaphase transition

Wei-Meng Zhao1, Judith A Coppinger, Akiko Seki

  • 1Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA.

Proceedings of the National Academy of Sciences of the United States of America
|September 2, 2008
PubMed

Insights

Researchers identified RCS1 as a key mitotic regulator controlling the metaphase-to-anaphase transition. RCS1

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • The anaphase-promoting complex/cyclosome (APC/C) is crucial for regulating cell cycle progression.
  • APC/C controls the metaphase-to-anaphase transition by degrading key proteins like securin.

Purpose of the Study:

  • To identify and characterize novel regulators of the metaphase-to-anaphase transition.
  • To elucidate the role of RCS1 in cell cycle control and its interaction with the APC/C.

Main Methods:

  • Cell cycle analysis to monitor RCS1 protein levels.
  • In vitro ubiquitination assays to assess APC/C activity on RCS1.
  • In vivo degradation studies and D-box mutant analysis.
  • Biochemical assays to identify RCS1-interacting complexes.

Main Results:

  • RCS1 levels peak in mitosis and decrease during G1 exit.
  • APC/C directly ubiquitinates RCS1 via a unique N-terminal D-box, leading to its degradation.
  • Loss of RCS1 accelerates the metaphase-to-anaphase transition and securin/cyclin B degradation.
  • Mitotic RCS1 associates with the NuRD chromatin-remodeling complex.

Conclusions:

  • RCS1 is a novel APC/C substrate and mitotic regulator controlling the timing of anaphase onset.
  • RCS1's interaction with the NuRD complex suggests a role in regulating gene expression or chromatin structure during mitosis.
  • This study reveals a new component in the regulatory network governing the metaphase-to-anaphase transition.

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