每年出版 6 期
ISSN 打印: 1040-8401
ISSN 在线: 2162-6472
Indexed in
Regulation of Thymocyte Survival by Transcriptional Coactivators
摘要
A majority of the developing T cells are eliminated by apoptosis because they do not meet the positive and negative selection criteria. Developing T cells are thus susceptible to apoptotic signals. On the other hand, there are mechanisms to prevent developing T cells from premature apoptosis. Maintenance of a fine balance between life and death is thus critical for successful completion of T-cell development. Our recent studies demonstrated an essential role of transcriptional coactivators in maintaining such a balance for developing T cells. Transcriptional coactivators are recruited by transcriptional factors to quantitatively regulate gene expression via modifying chromatin structure. Two transcriptional factors, TCF-1 and RORγt, are required to upregulate the levels of Bcl-xL, a critical survival factor for CD4+CD8+ double-positive thymocytes. However, TCF-1 and RORγt by themselves are not sufficient to stimulate Bcl-xL expression. Transcriptional coactivator β-catenin recruited by TCF-1, and steroid receptor coactivators (SRCs) recruited by RORγt, are also required for optimal stimulation of Bcl-xL expression. Thus, transcriptional coactivators are a substantial component of the transcriptional machinery to regulate thymocye survival, ensuring the completion of T-cell development.
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Wang Ruiqing, Xie Huimin, Huang Zhaofeng, Shang Weirong, Sun Zuoming, Developing and Activated T Cell Survival Depends on Differential Signaling Pathways to Regulate Anti-Apoptotic Bcl-xL, Clinical and Developmental Immunology, 2012, 2012. Crossref
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He Zhiheng, Wang Fei, Ma Jian, Sen Subha, Zhang Jing, Gwack Yousang, Zhou Yu, Sun Zuoming, Ubiquitination of RORγt at Lysine 446 Limits Th17 Differentiation by Controlling Coactivator Recruitment, The Journal of Immunology, 197, 4, 2016. Crossref
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Ma Jian, Wang Ruiqing, Fang Xianfeng, Ding Yan, Sun Zuoming, Spilianakis Charalampos Babis, Critical Role of TCF-1 in Repression of the IL-17 Gene, PLoS ONE, 6, 9, 2011. Crossref
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He Zhiheng, Ma Jian, Wang Ruiqing, Zhang Jing, Huang Zhaofeng, Wang Fei, Sen Subha, Rothenberg Ellen V, Sun Zuoming, A two-amino-acid substitution in the transcription factor RORγt disrupts its function in TH17 differentiation but not in thymocyte development, Nature Immunology, 18, 10, 2017. Crossref
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He Zhiheng, Wang Fei, Zhang Jing, Sen Subha, Pang Qihua, Luo Shengwei, Gwack Yousang, Sun Zuoming, Regulation of Th17 Differentiation by IKKα-Dependent and -Independent Phosphorylation of RORγt, The Journal of Immunology, 199, 3, 2017. Crossref
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He Zhiheng, Zhang Jing, Huang Zhaofeng, Du Qian, Li Ning, Zhang Qiang, Chen Yuan, Sun Zuoming, Sumoylation of RORγt regulates TH17 differentiation and thymocyte development, Nature Communications, 9, 1, 2018. Crossref
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Huang Zhaofeng, Wang Ruiqing, Xie Huimin, Shang Weirong, Manicassamy Santhakumar, Sun Zuoming, Stabilized β-Catenin Potentiates Fas-Mediated T Cell Apoptosis, The Journal of Immunology, 180, 10, 2008. Crossref
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Wang Ruiqing, Xie Huimin, Huang Zhaofeng, Ma Jian, Fang Xianfeng, Ding Yan, Sun Zuoming, T Cell Factor 1 Regulates Thymocyte Survival via a RORγt-Dependent Pathway, The Journal of Immunology, 187, 11, 2011. Crossref
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Wei Fengjiao, Zhou Xiaoqing, Chen Huanpeng, Tian Xuyan, Liu Zhonghua, Yu Bolan, He Xixin, Bai Chuan, Huang Zhaofeng, 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivative attenuates lupus nephritis with less effect to thymocyte development, Immunologic Research, 69, 4, 2021. Crossref
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Ligons Davinna L., Hwang SuJin, Waickman Adam T., Park Joo-Young, Luckey Megan A., Park Jung-Hyun, RORγt limits the amount of the cytokine receptor γc through the prosurvival factor Bcl-x L in developing thymocytes , Science Signaling, 11, 545, 2018. Crossref
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Ma Jian, Wang Ruiqing, Fang Xianfeng, Sun Zuoming, β-Catenin/TCF-1 Pathway in T Cell Development and Differentiation, Journal of Neuroimmune Pharmacology, 7, 4, 2012. Crossref