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
Summary
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 interactionMore Related Videos
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