{"doi":"10.1093/jimmun/vkaf283.304","title":"CBL-b regulates the protein stability of lupus susceptibility gene PBX1 2379","abstract":"Abstract Description Pre-B cell leukemia homeobox1 (PBX1) regulates gene expression by controlling chromatin accessibility. The expression of PBX1-D, a dominant negative splice isoform in CD4+ T cells, promotes lupus phenotypes. Among CD4+ T cells, PBX1 and PBX1-D are preferentially expressed in Treg cells among CD4+ T cells at the transcript and protein levels, and we have shown that Pbx1-deficiency altered Treg maintenance and function. PBX1-D protein is less stable than the normal isoform, PBX1-B, and it is degraded through the ubiquitin-proteasome-dependent pathway. Interestingly, CBL-b, E3 ubiquitin ligase functioning as a negative regulator of T cell activation, is downregulated in SLE CD4+ T cells. Here we showed that CBL-b is highly expressed in Treg cells and that it directly interacts with PBX1 and leads to Ub-mediated protein degradation. Cbl-b overexpression significantly decreased either PBX1-B or PBX1-D protein. In addition, mass spectrometry has identified TRIM21, another E3 Ub ligase, as a PBX1 binding partner with a weaker binding to PBX1-D. The relative abundance of the PBX1-D isoform in Tregs therefore integrates its interaction with E3 Ub ligases and their level of expression. Additional studies are on-going to further delineate the molecules involved in PBX1 protein expression in SLE T cells. Funding Sources This work was supported by National Institutes of Health Grants AI045050 Topic Categories Basic Autoimmunity (BA)","journal":"The Journal of Immunology","year":2025,"id":582414,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":456371,"name":"Seung‐Chul Choi","orcid":"0000-0001-6230-9087","position":1,"is_corresponding":false},{"id":302973,"name":"Laurence Morel","orcid":"0000-0002-6622-1290","position":2,"is_corresponding":false},{"id":863477,"name":"Yuk Pheel Park","orcid":"0000-0001-9749-5983","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:58:55.657290Z","pmid":null,"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":[]}