{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Stormo AED"],"funding":["NIA NIH HHS","NCRR NIH HHS","Laurel Endowment","Fondo di Ateneo per la Ricerca","UCSF Parnassus Flow Cytometry Core","National Institutes of Health","Fondazione Banco di Sardegna","Stowers Family Endowed Chair for Dental & Mineralized Tissue Research","NEI NIH HHS","NIDDK NIH HHS","DoD","NINDS NIH HHS","NCI NIH HHS","American Federation for Aging Research","DRC Center","Taube Koret Center","Michael J Fox Foundation","NIH HHS"],"pagination":["e202010065"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8919618"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["221(4)"],"pubmed_abstract":["Missense mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD); however, pathways regulating LRRK2 subcellular localization, function, and turnover are not fully defined. We performed quantitative mass spectrometry-based interactome studies to identify 48 novel LRRK2 interactors, including the microtubule-associated E3 ubiquitin ligase TRIM1 (tripartite motif family 1). TRIM1 recruits LRRK2 to the microtubule cytoskeleton for ubiquitination and proteasomal degradation by binding LRRK2911-919, a nine amino acid segment within a flexible interdomain region (LRRK2853-981), which we designate the \"regulatory loop\" (RL). Phosphorylation of LRRK2 Ser910/Ser935 within LRRK2 RL influences LRRK2's association with cytoplasmic 14-3-3 versus "],"journal":["The Journal of cell biology"],"pubmed_title":["The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity."],"pmcid":["PMC8919618"],"funding_grant_id":["SCR_018206","R01 EY027810","P30 DK063720","R01 CA219815","K08NS090633","R01 NS107480","S10 RR026758","R01 NS124848","RF1 AG058476","K08 NS090633","2014.0489","R01CA219815","RF1 NS124848","P01 AG054407","R01EY027810","W81XWH-18-1-0376","NIG P30 DK063720"],"pubmed_authors":["Earley EM","Cox TC","Skibinski G","van Haren J","Von Dollen J","FitzGibbon M","Dauer WT","Lum LS","Finkbeiner S","Hiniker A","Wittmann T","Crosio C","Ahrendt H","Johnson JR","Stormo AED","Shavarebi F","Krogan NJ","Davis EJ","Mirescu C","Porath J","Verschueren E","Iaccarino C","Oakes SA","Swaney DL","Ravisankar A","Balen C","Nichols RJ"],"additional_accession":[]},"is_claimable":false,"name":"The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity.","description":"Missense mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD); however, pathways regulating LRRK2 subcellular localization, function, and turnover are not fully defined. We performed quantitative mass spectrometry-based interactome studies to identify 48 novel LRRK2 interactors, including the microtubule-associated E3 ubiquitin ligase TRIM1 (tripartite motif family 1). TRIM1 recruits LRRK2 to the microtubule cytoskeleton for ubiquitination and proteasomal degradation by binding LRRK2911-919, a nine amino acid segment within a flexible interdomain region (LRRK2853-981), which we designate the \"regulatory loop\" (RL). Phosphorylation of LRRK2 Ser910/Ser935 within LRRK2 RL influences LRRK2's association with cytoplasmic 14-3-3 versus ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2026-05-31T05:00:55.991Z","creation":"2025-02-19T01:53:42.02Z"},"accession":"S-EPMC8919618","cross_references":{"pubmed":["35266954"],"doi":["10.1083/jcb.202010065"]}}