{"doi":"10.1016/j.neuron.2022.11.016","title":"Disruption of the ATXN1-CIC complex reveals the role of additional nuclear ATXN1 interactors in spinocerebellar ataxia type 1","abstract":"Spinocerebellar ataxia type 1 (SCA1) is a paradigmatic neurodegenerative disease in that it is caused by a mutation in a broadly expressed protein, ATXN1; however, only select populations of cells degenerate. The interaction of polyglutamine-expanded ATXN1 with the transcriptional repressor CIC drives cerebellar Purkinje cell pathogenesis; however, the importance of this interaction in other vulnerable cells remains unknown. Here, we mutated the 154Q knockin allele of Atxn1 154Q/2Q mice to prevent the ATXN1-CIC interaction globally. This normalized genome-wide CIC binding; however, it only partially corrected transcriptional and behavioral phenotypes, suggesting the involvement of additional factors in disease pathogenesis. Using unbiased proteomics, we identified three ATXN1-interacting transcription factors: RFX1, ZBTB5, and ZKSCAN1. We observed altered expression of RFX1 and ZKSCAN1 target genes in SCA1 mice and patient-derived iNeurons, highlighting their potential contributions to disease. Together, these data underscore the complexity of mechanisms driving cellular vulnerability in SCA1.","journal":"Neuron","year":2022,"id":249640,"datarank":0.5050943744979712,"base_score":3.367295829986474,"endowment":3.367295829986474,"self_citation_contribution":0.5050943744979712,"citation_network_contribution":0.0,"self_endowment_contribution":0.5050943744979712,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":28,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9501,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":346701,"name":"Mark A. Durham","orcid":null,"position":1,"is_corresponding":false},{"id":552364,"name":"Larissa Nitschke","orcid":"0000-0002-8040-2100","position":2,"is_corresponding":false},{"id":553233,"name":"Eder Xhako","orcid":null,"position":3,"is_corresponding":false},{"id":330712,"name":"Amanda M Brown","orcid":"0000-0002-1484-8972","position":4,"is_corresponding":false},{"id":890447,"name":"Jean‐Pierre Revelli","orcid":"0000-0002-4789-3104","position":5,"is_corresponding":false},{"id":890448,"name":"Esmeralda Villavicencio Gonzalez","orcid":"0000-0001-8153-8432","position":6,"is_corresponding":false},{"id":271029,"name":"Tao Lin","orcid":"0000-0002-6441-067X","position":7,"is_corresponding":false},{"id":497796,"name":"Hillary P. Handler","orcid":"0000-0001-5757-4548","position":8,"is_corresponding":false},{"id":274979,"name":"Yanwan Dai","orcid":"0000-0002-4485-4396","position":9,"is_corresponding":false},{"id":345825,"name":"Alexander J. Trostle","orcid":"0000-0001-5028-0184","position":10,"is_corresponding":false},{"id":110454,"name":"Ying‐Wooi Wan","orcid":"0000-0002-4354-7482","position":11,"is_corresponding":false},{"id":110460,"name":"Zhandong Liu","orcid":"0000-0002-7608-0831","position":12,"is_corresponding":false},{"id":271032,"name":"Roy V. Sillitoe","orcid":"0000-0002-6177-6190","position":13,"is_corresponding":false},{"id":262866,"name":"Harry T. Orr","orcid":"0000-0001-6118-741X","position":14,"is_corresponding":false},{"id":24573,"name":"Huda Y. Zoghbi","orcid":"0000-0002-0700-3349","position":15,"is_corresponding":false},{"id":552366,"name":"Stephanie L. Coffin","orcid":"0000-0002-9119-0377","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:24:23.754337Z","pmid":"36577402","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":[]}