Evidence map›Paper›PMID 38395307›Full record

ArticleThe Journal of biological chemistry2024

SUMO modifies GβL and mediates mTOR signaling.

Sophia Louise Lucille Park, Uri Nimrod Ramírez-Jarquín, Neelam Shahani, Oscar Rivera, Manish Sharma, Preksha Sandipkumar Joshi, Aayushi Hansalia, Sunayana Dagar, Francis P McManus, Pierre Thibault and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.9field-weighted citation impact, top 28% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 2 countries.

Sophia Louise Lucille ParkDepartment of Neuroscience, The Wertheim UF Scripps Institute, Jupiter, Florida, USA.
Uri Nimrod Ramírez-JarquínDepartment of Neuroscience, The Wertheim UF Scripps Institute, Jupiter, Florida, USA.
Neelam ShahaniDepartment of Neuroscience, The Wertheim UF Scripps Institute, Jupiter, Florida, USA.
Oscar RiveraDepartment of Neuroscience, The Wertheim UF Scripps Institute, Jupiter, Florida, USA.
Manish SharmaDepartment of Neuroscience, The Wertheim UF Scripps Institute, Jupiter, Florida, USA.
Preksha Sandipkumar JoshiDepartment of Neuroscience, The Wertheim UF Scripps Institute, Jupiter, Florida, USA.
Aayushi HansaliaDepartment of Neuroscience, The Wertheim UF Scripps Institute, Jupiter, Florida, USA.
Sunayana DagarDepartment of Neuroscience, The Wertheim UF Scripps Institute, Jupiter, Florida, USA.
Francis P McManusInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, Quebec, Canada.
Pierre ThibaultInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, Quebec, Canada; Department of Chemistry, Université de Montréal, Montréal, Quebec, Canada.
Srinivasa SubramaniamDepartment of Neuroscience, The Wertheim UF Scripps Institute, Jupiter, Florida, USA; The Skaggs Graduate School of Chemical and Biological Sciences, The Scripps Research Institute, La Jolla, California, USA; Norman Fixel Institute for Neurological Diseases, Gainesville, Florida, USA. Electronic address: subramaniams@ufl.edu.
Scripps Research Institute · USInstitute for Research in Immunology and Cancer · CA

Funding

mTOR Signaling in Striatum: Regulation and FunctionR01NS087019 · NINDS · SCRIPPS FLORIDA · PI SUBRAMANIAM, SRINI · 2015 to 2019
$2.3M
Rhes-SUMO Pathway in Huntington DiseaseR01NS128225 · NINDS · UNIVERSITY OF FLORIDA · PI Srinivasa Subramaniam · 2022 to 2026
$1.9M
Rhes-SUMO circuitry in Huntington's Disease PathogenesisR01NS094577 · NINDS · SCRIPPS FLORIDA · PI SUBRAMANIAM, SRINI · 2016 to 2019
$1.7M
Mechanisms of Translational Dysregulation in Huntington DiseaseR01NS138278 · NINDS · UNIVERSITY OF FLORIDA · PI Srinivasa Subramaniam · 2024 to 2026
$1.2M
Validating cGAS-STING pathway as drug target in Huntington disease mouse modelR21NS128564 · NINDS · UNIVERSITY OF FLORIDA · PI SUBRAMANIAM, SRINI · 2022 to 2022
$531k
NINDS NIH HHS R01 NS087019NINDS NIH HHS R01 NS094577NINDS NIH HHS R01 NS128225NINDS NIH HHS R01 NS138278NINDS NIH HHS R21 NS128564
6 · The paper itself

Abstract

The mechanistic target of rapamycin (mTOR) signaling is influenced by multiple regulatory proteins and post-translational modifications; however, underlying mechanisms remain unclear. Here, we report a novel role of small ubiquitin-like modifier (SUMO) in mTOR complex assembly and activity. By investigating the SUMOylation status of core mTOR components, we observed that the regulatory subunit, GβL (G protein β-subunit-like protein, also known as mLST8), is modified by SUMO1, 2, and 3 isoforms. Using mutagenesis and mass spectrometry, we identified that GβL is SUMOylated at lysine sites K86, K215, K245, K261, and K305. We found that SUMO depletion reduces mTOR-Raptor (regulatory protein associated with mTOR) and mTOR-Rictor (rapamycin-insensitive companion of mTOR) complex formation and diminishes nutrient-induced mTOR signaling. Reconstitution with WT GβL but not SUMOylation-defective KR mutant GβL promotes mTOR signaling in GβL-depleted cells. Taken together, we report for the very first time that SUMO modifies GβL, influences the assembly of mTOR protein complexes, and regulates mTOR activity.

Indexed as

Signal TransductionSumoylationTOR Serine-Threonine KinasesHEK293 CellsHumansLysinemTOR Associated Protein, LST8 HomologSmall Ubiquitin-Related Modifier ProteinsSUMO-1 ProteinUbiquitinsLysinemTOR Associated Protein, LST8 HomologMTOR protein, humanSmall Ubiquitin-Related Modifier ProteinsSUMO-1 ProteinSUMO1 protein, humanSUMO2 protein, humanSUMO3 protein, humanTOR Serine-Threonine KinasesUbiquitinsamino acid stimulationkinase signalinglysine-site regulationnutrient signalingpost-translational modificationprotein–protein interactionSUMO interactive motifSUMO isoformsSUMO mechanism

Identifiers

PMID38395307
PMCPMC10982569
OpenAlexW4392015055

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.