{"doi":"10.1016/j.jbc.2024.105778","title":"SUMO modifies GβL and mediates mTOR signaling","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.","journal":"Journal of Biological Chemistry","year":2024,"id":464888,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":413935,"name":"Uri Nimrod Ramírez-Jarquín","orcid":"0000-0002-0752-1293","position":1,"is_corresponding":false},{"id":413936,"name":"Neelam Shahani","orcid":"0000-0003-1907-4811","position":2,"is_corresponding":false},{"id":560431,"name":"Oscar Rivera","orcid":"0000-0002-4509-4341","position":3,"is_corresponding":false},{"id":560432,"name":"Manish Sharma","orcid":"0000-0001-6103-4368","position":4,"is_corresponding":false},{"id":1233697,"name":"Preksha Sandipkumar Joshi","orcid":null,"position":5,"is_corresponding":false},{"id":1296075,"name":"Aayushi Hansalia","orcid":null,"position":6,"is_corresponding":false},{"id":784958,"name":"Sunayana Dagar","orcid":"0000-0002-5070-9232","position":7,"is_corresponding":false},{"id":561199,"name":"Francis P. McManus","orcid":null,"position":8,"is_corresponding":false},{"id":304775,"name":"Pierre Thibault","orcid":"0000-0001-5993-0331","position":9,"is_corresponding":false},{"id":411870,"name":"Srinivasa Subramaniam","orcid":"0000-0002-7428-4953","position":10,"is_corresponding":false},{"id":400663,"name":"Sophia Park","orcid":"0000-0002-1615-1749","position":0,"is_corresponding":true}],"reference_count":74,"raw_metadata":null,"created_at":"2026-07-19T02:04:42.082401Z","pmid":"38395307","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}