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Rack1 protects N-terminal phosphorylated c-Jun from Fbw7-mediated degradation

J Zhang1, F Zhu, X Li

  • 1Department of Cellular and Molecular Biology, The Hormel Institute, University of Minnesota, Austin, 55912, USA.

Oncogene
|August 24, 2011
PubMed

Insights

Receptor for activated C-kinase 1 (Rack1) stabilizes phosphorylated c-Jun by releasing it from the Fbw7 ubiquitin ligase complex, preventing degradation and promoting cancer cell growth.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cellular Signaling

Background:

  • The transcription factor c-Jun is a known oncoprotein that is typically unstable and targeted for degradation by ubiquitin ligases.
  • Phosphorylation of c-Jun by kinases like JNKs stabilizes it by reducing ubiquitination, but the mechanism remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which N-terminal phosphorylation stabilizes c-Jun.
  • To investigate the role of Rack1 in the regulation of c-Jun stability and degradation.

Main Methods:

  • Co-immunoprecipitation assays to detect protein-protein interactions.
  • Western blotting to assess protein levels and ubiquitination status.
  • Cellular assays to monitor c-Jun stability and accumulation.

Main Results:

  • Rack1 forms a complex with both c-Jun and the ubiquitin ligase Fbw7.
  • N-terminal phosphorylation of c-Jun causes its release from the Rack1-Fbw7 complex.
  • Release from the complex prevents Fbw7-mediated ubiquitination, leading to c-Jun stabilization and accumulation.

Conclusions:

  • Rack1 acts as a scaffold, mediating the interaction between c-Jun and Fbw7.
  • Phosphorylation-dependent release of c-Jun from this complex is a key mechanism for its stabilization.
  • Rack1 plays a critical role in tumorigenesis by controlling the stability of phosphorylated c-Jun.

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