{"doi":"10.1111/febs.16766","title":"CARPs regulate STUB1 and its pathogenic mutants aggregation kinetics by mono‐ubiquitination","abstract":"The development of neurological pathologies is linked to the accumulation of protein aggregates like alpha-synuclein in Parkinson's disease and tau protein in Alzheimer's disease. Mono- or di-ubiquitination of these molecules has been reported to stabilize aggregates and contribute to the disorders. STIP1 Homologous and U-Box-containing protein 1 (STUB1) is a multifunctional protein that maintains proteostasis and insulin signalling. In spinocerebellar ataxia 16 (SCAR16), an autosomal recessive neurodegenerative disease, mutations in and aggregation of STUB1 are reported. Despite the well-accepted neuroprotective role of STUB1, very little is known of regulatory mechanisms that control the dynamics of STUB1 aggregate assembly. Here, we report that CARP2, a ubiquitin ligase, is a novel regulator of STUB1. CARP2 interacts and mono-ubiquitinates STUB1. Furthermore, we found that CARP2 regulates STUB1 through its TPR motif, a domain that is also associated with HSP70. Modification of STUB1 by CARP2 leads to detergent-insoluble aggregate formation. Importantly, pathogenic mutants of STUB1 are more prone than the wild-type to CARP2-mediated aggregate assembly. Hence our findings revealed CARPs (CARP1 & CARP2) as novel regulators of STUB1 and controlled its cytosolic versus aggregate dynamics.","journal":"FEBS Journal","year":2023,"id":381587,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9457,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1147962,"name":"Prema Mondal","orcid":null,"position":1,"is_corresponding":false},{"id":72070,"name":"Srinivasa M. Srinivasula","orcid":"0000-0003-4804-6916","position":2,"is_corresponding":false},{"id":1147586,"name":"R. N. Sharma","orcid":"0000-0002-6504-0578","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":null,"created_at":"2026-07-19T01:17:12.933204Z","pmid":"36853170","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":[]}