Related Experiment Video

Updated: Jul 2, 2025

Utilizing a Comprehensive Immunoprecipitation Enrichment System to Identify an Endogenous Post-translational Modification Profile for Target Proteins
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Utilizing a Comprehensive Immunoprecipitation Enrichment System to Identify an Endogenous Post-translational Modification Profile for Target Proteins

Published on: January 8, 2018

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SUMO modifies GβL and mediates mTOR signaling

Sophia Louise Lucille Park1, Uri Nimrod Ramírez-Jarquín1, Neelam Shahani1

  • 1Department of Neuroscience, The Wertheim UF Scripps Institute, Jupiter, Florida, USA.

The Journal of Biological Chemistry
|February 23, 2024
PubMed

Insights

Small ubiquitin-like modifier (SUMO) attaches to G protein β-subunit-like protein (GβL), impacting mechanistic target of rapamycin (mTOR) complex assembly and signaling. This SUMOylation is crucial for nutrient-induced mTOR pathway activation.

Area of Science:

  • Cellular signaling pathways
  • Post-translational modifications
  • Protein complex assembly

Background:

  • Mechanistic target of rapamycin (mTOR) signaling is vital for cell growth and metabolism.
  • mTOR regulation involves numerous proteins and post-translational modifications, but mechanisms are not fully understood.
  • Small ubiquitin-like modifier (SUMO) is a key post-translational modification influencing protein function.

Purpose of the Study:

  • To investigate the role of SUMOylation in the assembly and activity of mTOR complexes.
  • To identify which mTOR components are SUMOylated and the specific sites of modification.

Main Methods:

  • Investigated SUMOylation status of core mTOR components using biochemical assays.
  • Identified SUMOylation sites on GβL (mLST8) using mutagenesis and mass spectrometry.
  • Assessed the impact of SUMO depletion and GβL SUMOylation mutants on mTOR complex formation and signaling.

Main Results:

  • The regulatory subunit GβL (mLST8) is SUMOylated by SUMO1, 2, and 3 isoforms at multiple lysine residues (K86, K215, K245, K261, K305).
  • SUMOylation of GβL is essential for the formation of mTOR-Raptor and mTOR-Rictor complexes.
  • Depletion of SUMO or use of SUMOylation-defective GβL mutants impairs nutrient-induced mTOR signaling.

Conclusions:

  • This study reveals a novel role for SUMOylation in regulating mTOR signaling.
  • SUMOylation of GβL is critical for the proper assembly of mTOR complexes (mTORC1 and mTORC2).
  • SUMO modification of GβL directly influences mTOR pathway activity and nutrient sensing.
Keywords:
SUMO interactive motifSUMO isoformsSUMO mechanismamino acid stimulationkinase signalinglysine-site regulationnutrient signalingpost-translational modificationprotein–protein interaction

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