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Anaphase-promoting complex/cyclosome-cdh1 mediates the ubiquitination and degradation of TRB3

Nobumichi Ohoka1, Satoshi Sakai, Kikuo Onozaki

  • 1Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.

Biochemical and Biophysical Research Communications
|January 13, 2010
PubMed

Insights

TRB3 protein stability is controlled by the ubiquitin-proteasome system. The anaphase-promoting complex/cyclosome (APC/C) with Cdh1 targets TRB3 for degradation, regulating its levels during endoplasmic reticulum stress.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • TRB3 is an endoplasmic reticulum (ER) stress-inducible protein regulated by CHOP and ATF4.
  • The precise mechanisms controlling TRB3 protein stability and function remain largely uncharacterized.

Purpose of the Study:

  • To elucidate the regulatory mechanisms governing TRB3 protein stability.
  • To investigate the role of the ubiquitin-proteasome system in TRB3 degradation.

Main Methods:

  • Protein stability assays using TRB3 mutants (D-box deletion).
  • Co-immunoprecipitation to assess interactions with APC/C components (Cdc20, Cdh1).
  • Western blotting to analyze protein expression levels and ubiquitination following Cdh1 manipulation.

Main Results:

  • TRB3 is an unstable protein targeted for degradation by the ubiquitin-proteasome system.
  • The carboxyl-terminal D-box motif of TRB3 is essential for its degradation.
  • TRB3 interacts with APC/C coactivators Cdc20 and Cdh1, with Cdh1 specifically mediating TRB3 downregulation and ubiquitination.

Conclusions:

  • The anaphase-promoting complex/cyclosome (APC/C) complexed with Cdh1 (APC/C(Cdh1)) ubiquitinates and degrades TRB3 protein.
  • APC/C(Cdh1)-mediated degradation is a key mechanism for regulating TRB3 stability, particularly in the context of ER stress.

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