{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sharma J"],"funding":["NICHD NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke","Beyond Batten Disease Foundation","NIMH NIH HHS","NINDS NIH HHS","U.S. Department of Health & Human Services | National Institutes of Health"],"pagination":["32"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10038992"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(1)"],"pubmed_abstract":["Calpains are a class of non-lysosomal cysteine proteases that exert their regulatory functions via limited proteolysis of their substrates. Similar to the lysosomal and proteasomal systems, calpain dysregulation is implicated in the pathogenesis of neurodegenerative disease and cancer. Despite intensive efforts placed on the identification of mechanisms that regulate calpains, however, calpain protein modifications that regulate calpain activity are incompletely understood. Here we show that calpains are regulated by KCTD7, a cytosolic protein of previously uncharacterized function whose pathogenic mutations result in epilepsy, progressive ataxia, and severe neurocognitive deterioration. We show that KCTD7 works in complex with Cullin-3 and Rbx1 to execute atypical, non-degradative ubiquit"],"journal":["Cell discovery"],"pubmed_title":["Calpain activity is negatively regulated by a KCTD7-Cullin-3 complex via non-degradative ubiquitination."],"pmcid":["PMC10038992"],"funding_grant_id":["N/A","1U54 HD083092","P50 HD103555","U54 HD083092","R01 NS062829","NS079618","R56 NS079618","R01 NS079618","RF1 NS062829","R01 MH109511"],"pubmed_authors":["Xiong Y","Tolias KF","Bajaj L","Sardiello M","Goo YA","Leung HE","Mulherkar S","Sharma J","Chen UI","Cho BK"],"additional_accession":[]},"is_claimable":false,"name":"Calpain activity is negatively regulated by a KCTD7-Cullin-3 complex via non-degradative ubiquitination.","description":"Calpains are a class of non-lysosomal cysteine proteases that exert their regulatory functions via limited proteolysis of their substrates. Similar to the lysosomal and proteasomal systems, calpain dysregulation is implicated in the pathogenesis of neurodegenerative disease and cancer. Despite intensive efforts placed on the identification of mechanisms that regulate calpains, however, calpain protein modifications that regulate calpain activity are incompletely understood. Here we show that calpains are regulated by KCTD7, a cytosolic protein of previously uncharacterized function whose pathogenic mutations result in epilepsy, progressive ataxia, and severe neurocognitive deterioration. We show that KCTD7 works in complex with Cullin-3 and Rbx1 to execute atypical, non-degradative ubiquit","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Mar","modification":"2026-05-28T17:56:30.178Z","creation":"2025-02-18T23:23:30.237Z"},"accession":"S-EPMC10038992","cross_references":{"pubmed":["36964131"],"doi":["10.1038/s41421-023-00533-3"]}}