The phosphatase-transcription activator EYA1 is targeted by anaphase-promoting complex/Cdh1 for degradation at

Jianbo Sun1, Zoi Karoulia, Elaine Y M Wong

  • 1Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA.

Insights

EYA1 protein levels are tightly controlled during the cell cycle through degradation. The anaphase-promoting complex/cyclosome (APC/C)-Cdh1 complex targets EYA1 for destruction during the M-to-G(1) transition.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • EYA1 protein is overexpressed in cancers and crucial for mammalian organogenesis.
  • Regulation of EYA1 during development remains largely unknown.
  • EYA1 is essential for cell proliferation and survival.

Purpose of the Study:

  • To investigate the regulatory mechanisms controlling EYA1 protein levels during the cell cycle.
  • To elucidate how EYA1 is degraded and its role in cell cycle progression.

Main Methods:

  • Cell cycle analysis to monitor EYA1 protein levels.
  • Ubiquitin-mediated proteolysis assays.
  • Co-immunoprecipitation to study protein interactions.
  • RNA interference to deplete Cdh1.
  • Western blotting to assess protein levels.

Main Results:

  • EYA1 protein levels fluctuate during the cell cycle, peaking in mitosis and decreasing during G(1).
  • EYA1 undergoes degradation during mitotic exit in a Cdh1-dependent manner.
  • Cdh1 directly interacts with EYA1.
  • Overexpression of Cdh1 reduces EYA1 levels, while Cdh1 depletion stabilizes EYA1.

Conclusions:

  • The anaphase-promoting complex/cyclosome (APC/C)-Cdh1 specifically targets EYA1 for degradation during the M-to-G(1) transition.
  • Failure in EYA1 degradation may impact cell proliferation and survival.
  • This study reveals a novel regulatory mechanism for EYA1 crucial for cell cycle control.

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