{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T22:58:49Z","timestamp":1778108329061,"version":"3.51.4"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K07459"],"award-info":[{"award-number":["20K07459"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"MEXT | Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19H04820"],"award-info":[{"award-number":["19H04820"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Posttranslational modification, such as phosphorylation, is an important biological event that modulates and diversifies protein function. Bcl11b protein is a zinc-finger transcription factor that plays a crucial role in early T cell development and the segregation of T cell subsets. Bcl11b possesses at least 25 serine\/threonine (S\/T) residues that can be phosphorylated upon TCR stimulation. To understand the physiological relevance of the phosphorylation on Bcl11b protein, we replaced S\/T residues with alanine (A) by targeting murine Bcl11b gene in embryonic stem cells. By combinational targeting of exons 2 and 4 in the Bcl11b gene, we generated a mouse strain, Bcl11b-phosphorylation site mutation mice, in which 23 S\/T residues were replaced with A residues. Such extensive manipulation left only five putative phosphorylated residues, two of which were specific for mutant protein, and resulted in reduced amounts of Bcl11b protein. However, primary T cell development in the thymus, as well as the maintenance of peripheral T cells, remained intact even after loss of major physiological phosphorylation. In addition, in\u00a0vitro differentiation of CD4+ naive T cells into effector Th cell subsets\u2014Th1, Th2, Th17, and regulatory T\u2014was comparable between wild-type and Bcl11b-phosphorylation site mutation mice. These findings indicate that the physiological phosphorylation on major 23 S\/T residues in Bcl11b is dispensable for Bcl11b functions in early T cell development and effector Th cell differentiation.<\/jats:p>","DOI":"10.4049\/jimmunol.2200101","type":"journal-article","created":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T13:52:43Z","timestamp":1681912363000},"page":"1728-1739","source":"Crossref","is-referenced-by-count":1,"title":["The Majority of the Serine\/Threonine Phosphorylation Sites in Bcl11b Protein Are Dispensable for the Differentiation of T Cells"],"prefix":"10.1093","volume":"210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0262-9326","authenticated-orcid":false,"given":"Kazuki","family":"Okuyama","sequence":"first","affiliation":[{"name":"Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences , Tsurumi-ku, Yokohama, Kanagawa,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0572-2358","authenticated-orcid":false,"given":"Aneela","family":"Nomura","sequence":"additional","affiliation":[{"name":"Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences , Tsurumi-ku, Yokohama, Kanagawa,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohei","family":"Nishino","sequence":"additional","affiliation":[{"name":"Division of Cell Signaling, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University , Tokushima,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences , Tsurumi-ku, Yokohama, Kanagawa,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8045-9166","authenticated-orcid":false,"given":"Christelle","family":"Harly","sequence":"additional","affiliation":[{"name":"Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences , Tsurumi-ku, Yokohama, Kanagawa,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Risa","family":"Chihara","sequence":"additional","affiliation":[{"name":"Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences , Tsurumi-ku, Yokohama, Kanagawa,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasuyo","family":"Harada","sequence":"additional","affiliation":[{"name":"Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences , Tsurumi-ku, Yokohama, Kanagawa,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sawako","family":"Muroi","sequence":"additional","affiliation":[{"name":"Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences , Tsurumi-ku, Yokohama, Kanagawa,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Kubo","sequence":"additional","affiliation":[{"name":"Laboratory for Cytokine Regulation, RIKEN Center for Integrative Medical Sciences , Tsurumi-ku, Yokohama, Kanagawa,","place":["Japan"]},{"name":"Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science , Noda-shi, Chiba 278-0022,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3228-6368","authenticated-orcid":false,"given":"Hidetaka","family":"Kosako","sequence":"additional","affiliation":[{"name":"Division of Cell Signaling, Fujii Memorial Institute of Medical Sciences, Institute of Advanced Medical Sciences, Tokushima University , Tokushima,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9853-9068","authenticated-orcid":false,"given":"Ichiro","family":"Taniuchi","sequence":"additional","affiliation":[{"name":"Laboratory for Transcriptional Regulation, RIKEN Center for Integrative Medical Sciences , Tsurumi-ku, Yokohama, Kanagawa,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"2025021008060262300_r1","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.gpb.2018.06.004","article-title":"PTMD: a database of human disease-associated post-translational modifications","volume":"16","author":"Xu","year":"2018","journal-title":"Genomics Proteomics Bioinformatics"},{"key":"2025021008060262300_r2","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1016\/j.drudis.2020.06.005","article-title":"Targeting post-translational modification of transcription factors as cancer therapy","volume":"25","author":"Qian","year":"2020","journal-title":"Drug Discov. 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