{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ordureau A"],"funding":["Cancer Research Society/BMO Bank of Montreal Scholarship for the Next Generation of Scientists","NIDDK NIH HHS","Genome Canada Disruptive Innovation in Genomics","Michael J. Fox Foundation","NINDS NIH HHS","NIH","Edward R. and Anne G. Lefler Center Postdoctoral Fellowship","Harvard Medical School Cell Biology Initiative for Molecular Trafficking and Neurodegeneration","Sara Elizabeth O’Brien Trust Postdoctoral Fellowship","NIGMS NIH HHS","Ned Goodnow"],"pagination":["211-227.e8"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC5910199"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["70(2)"],"pubmed_abstract":["Flux through kinase and ubiquitin-driven signaling systems depends on the modification kinetics, stoichiometry, primary site specificity, and target abundance within the pathway, yet we rarely understand these parameters and their spatial organization within cells. Here we develop temporal digital snapshots of ubiquitin signaling on the mitochondrial outer membrane in embryonic stem cell-derived neurons, and we model HeLa cell systems upon activation of the PINK1 kinase and PARKIN ubiquitin ligase by proteomic counting of ubiquitylation and phosphorylation events. We define the kinetics and site specificity of PARKIN-dependent target ubiquitylation, and we demonstrate the power of this approach to quantify pathway modulators and to mechanistically define the role of PARKIN UBL phosphorylat"],"journal":["Molecular cell"],"pubmed_title":["Dynamics of PARKIN-Dependent Mitochondrial Ubiquitylation in Induced Neurons and Model Systems Revealed by Digital Snapshot Proteomics."],"pmcid":["PMC5910199"],"funding_grant_id":["R01 GM095567","RO1 GM095567","OGI-119","11115.01","R37 NS083524","K01 DK098285","K01DK098285","RO1 GM067945","R01 GM067945"],"pubmed_authors":["Zhang W","Harper JW","Hou Z","Rubin LL","Zhang J","Paulo JA","Sidhu SS","Cohn EF","Gygi SP","Ahfeldt T","Ordureau A","Heo JM"],"additional_accession":[]},"is_claimable":false,"name":"Dynamics of PARKIN-Dependent Mitochondrial Ubiquitylation in Induced Neurons and Model Systems Revealed by Digital Snapshot Proteomics.","description":"Flux through kinase and ubiquitin-driven signaling systems depends on the modification kinetics, stoichiometry, primary site specificity, and target abundance within the pathway, yet we rarely understand these parameters and their spatial organization within cells. Here we develop temporal digital snapshots of ubiquitin signaling on the mitochondrial outer membrane in embryonic stem cell-derived neurons, and we model HeLa cell systems upon activation of the PINK1 kinase and PARKIN ubiquitin ligase by proteomic counting of ubiquitylation and phosphorylation events. We define the kinetics and site specificity of PARKIN-dependent target ubiquitylation, and we demonstrate the power of this approach to quantify pathway modulators and to mechanistically define the role of PARKIN UBL phosphorylat","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Apr","modification":"2026-04-29T09:56:43.834Z","creation":"2019-06-06T19:22:39Z"},"accession":"S-EPMC5910199","cross_references":{"pubmed":["29656925"],"doi":["10.1016/j.molcel.2018.03.012"]}}