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Akt activation promotes degradation of tuberin and FOXO3a via the proteasome

David R Plas1, Craig B Thompson

  • 1Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, Pennsylania 19104, USA.

The Journal of Biological Chemistry
|January 9, 2003
PubMed

Insights

Activated Akt (a protein kinase) triggers the proteasomal degradation of its substrates, promoting cell growth and survival. This process involves the breakdown of negative regulators, leading to enhanced cell proliferation and survival.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Growth factor receptors are crucial for cell growth and survival.
  • They activate phosphatidylinositol 3-kinase and Akt/PKB signaling pathways.
  • Understanding Akt's downstream effects is key to cellular regulation.

Purpose of the Study:

  • To investigate the role of Akt activation in protein degradation.
  • To identify Akt substrates targeted for proteasomal degradation.
  • To elucidate the mechanism of Akt-mediated cell growth and survival.

Main Methods:

  • Expression of activated Akt in cellular models.
  • Utilizing proteasome inhibitors to assess protein stability.
  • Analyzing protein levels and ubiquitination status of Akt substrates.
  • Western blotting and immunoprecipitation techniques.

Main Results:

  • Activated Akt induced proteasome-dependent degradation of tuberin, FOXO1, and FOXO3a.
  • Proteasome inhibitors stabilized phosphorylated Akt substrates.
  • Akt activation led to ubiquitination of proteins with phosphorylated Akt substrate motifs.

Conclusions:

  • Activated Akt promotes cell growth and survival via proteasomal degradation of its substrates.
  • This degradation targets negative regulators of cell growth and survival.
  • Akt-mediated proteolysis is a critical mechanism in cellular regulation.

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