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mTORC2 can associate with ribosomes to promote cotranslational phosphorylation and stability of nascent Akt

Won Jun Oh1, Chang-chih Wu, Sung Jin Kim

  • 1Department of Physiology and Biophysics, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA.

The EMBO Journal
|November 4, 2010
PubMed

Insights

Mammalian target of rapamycin complex 2 (mTORC2) phosphorylates nascent Akt protein during translation, preventing ubiquitination. This cotranslational modification by mTORC2 links protein synthesis to cellular quality control mechanisms.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Mechanisms coupling protein translation and processing in eukaryotes are not fully understood.
  • Mammalian target of rapamycin complex 1 (mTORC1) regulates translation initiation, but mTORC2's role in protein synthesis is undefined.

Purpose of the Study:

  • To investigate the function of mTORC2 in cotranslational protein processing.
  • To determine how mTORC2 interacts with ribosomes and nascent polypeptides.

Main Methods:

  • Immunofluorescence to assess mTORC2 and ribosome colocalization.
  • Co-immunoprecipitation to study mTORC2 and ribosomal protein interactions.
  • In vitro phosphorylation assays to examine Akt nascent chain modification.

Main Results:

  • mTORC2 colocalizes with actively translating ribosomes and interacts with ribosomal protein rpL23a.
  • mTORC2 cotranslationally phosphorylates nascent Akt at Thr450, preventing ubiquitination.
  • Phosphorylation site accessibility (turn motif vs. hydrophobic motif) dictates cotranslational modification.

Conclusions:

  • mTORC2 functions cotranslationally by modifying nascent polypeptide chains.
  • This cotranslational phosphorylation is critical for achieving proper protein conformation and preventing degradation.
  • The study reveals a novel link between mTOR signaling, protein synthesis, and cellular quality control.

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