{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T16:32:16Z","timestamp":1758990736559,"version":"3.37.3"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T00:00:00Z","timestamp":1690156800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI045050"],"award-info":[{"award-number":["R01 AI045050"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Pre\u2013B cell leukemia homeobox 1 (PBX1) controls chromatin accessibility to a large number of genes in various cell types. Its dominant negative splice isoform, PBX1D, which lacks the DNA and Hox-binding domains, is expressed more frequently in the CD4+ T cells from lupus-prone mice and patients with systemic lupus erythematosus than healthy control subjects. PBX1D overexpression in CD4+ T cells impaired regulatory T cell homeostasis and expanded inflammatory CD4+ T cells. In this study, we showed that PBX1 message expression is downregulated by activation in CD4+ T cells as well as in B cells. PBX1D protein was less stable than the normal isoform, PBX1B, and it is degraded through the ubiquitin-proteasome\u2013dependent pathway. The DNA binding domain lacking in PBX1D has two putative ubiquitin binding sites, K292 and K293, that are predicted to be in direct contact with DNA. Mutation of K292-293 reduced PBX1B stability to a level similar to PBX1D and abrogated DNA binding. In addition, contrary to PBX1B, PBX1D is retained in the cytoplasm without the help of the cofactors MEIS or PREP1, indicating a different requirement for nuclear translocation. Overall, these findings suggest that multiple post-transcriptional mechanisms are responsible for PBX1D loss of function and induction of CD4+ T cell inflammatory phenotypes in systemic lupus erythematosus.<\/jats:p>","DOI":"10.4049\/jimmunol.2300362","type":"journal-article","created":{"date-parts":[[2023,7,24]],"date-time":"2023-07-24T13:53:54Z","timestamp":1690206834000},"page":"727-734","source":"Crossref","is-referenced-by-count":3,"title":["Molecular Mechanisms of Lupus Susceptibility Allele PBX1D"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9749-5983","authenticated-orcid":false,"given":"Yuk Pheel","family":"Park","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health , San Antonio, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracoyia","family":"Roach","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9576-6524","authenticated-orcid":false,"given":"Sujung","family":"Soh","sequence":"additional","affiliation":[{"name":"Research Institute of Women\u2019s Health, Sookmyung Women\u2019s University , Yongsan-Gu, Seoul ,","place":["South Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leilani","family":"Zeumer-Spataro","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Chul","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health , San Antonio, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4696-875X","authenticated-orcid":false,"given":"David A","family":"Ostrov","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida , Gainesville, FL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4239-0804","authenticated-orcid":false,"given":"Young","family":"Yang","sequence":"additional","affiliation":[{"name":"Research Institute of Women\u2019s Health, Sookmyung Women\u2019s University , Yongsan-Gu, Seoul ,","place":["South Korea"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurence","family":"Morel","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of Texas Health , San Antonio, TX"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,7,24]]},"reference":[{"key":"2025020406080615300_r1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0065-2776(06)92001-X","article-title":"Systemic lupus erythematosus: multiple immunological phenotypes in a complex genetic disease","volume":"92","author":"Fairhurst","year":"2006","journal-title":"Adv. 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