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* Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan;
Laboratory for Developmental Biology, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan; and
Division of Molecular Genetics, The Netherlands Cancer Institute, Amsterdam, The Netherlands
The Polycomb group (PcG) gene products regulate the maintenance of the homeobox gene expression in Drosophila and vertebrates and also the cell cycle progression in thymocytes and Th2 cell differentiation in mature T cells. We herein studied the role of PcG gene bmi-1 product in Th1/Th2 cell differentiation and found that Bmi-1 facilitates Th2 cell differentiation in a Ring finger-dependent manner. Biochemical studies indicate that Bmi-1 interacts with GATA3 in T cells, which is dependent on the Ring finger of Bmi-1. The overexpression of Bmi-1 resulted in a decreased ubiquitination and an increased protein stability of GATA3. In bmi-1-deficient Th cells, the levels of Th2 cell differentiation decreased as the degradation and ubiquitination on GATA3 increased. Therefore, Bmi-1 plays a crucial role in the control of Th2 cell differentiation in a Ring finger-dependent manner by regulating GATA3 protein stability.
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1 This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology (Japan) (Grants-in-Aid for Scientific Research in Priority Areas 17016010 and 17047007; Scientific Research B 17390139 and Scientific Research C 18590466; Grant-in-Aid for Young Scientists 17790318; and Special Coordination Funds for Promoting Science and Technology), the Ministry of Health, Labor and Welfare (Japan), the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Immovation (Japan), the Japan Health Science Foundation, the Kanae Foundation, the Uehara Memorial Foundation, and the Mochida Foundation.
2 Address correspondence and reprint requests to Dr. Toshinori Nakayama, Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. E-mail address: tnakayama{at}faculty.chiba-u.jp
3 Abbreviations used in this paper: PcG, Polycomb group; bmi-1 deficient, bmi-1–/–; CHX, cycloheximide; dP/S, proline/serine rich region-deleted bmi-1; dRing, Ring finger-deleted bmi-1; HPRT, hypoxanthine phosphoribosyltransferase; PRC, Polycomb-repressive complex; Tg, transgenic; wt, wild type; NGFR, nerve growth factor receptor.
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