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Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 0.657 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v26.i6.10
pages 475-486

Regulation of Thymocyte Survival by Transcriptional Coactivators

Huimin Xie
Department of Microbiology & Immunology, College of Medicine, University of Illinois, Chicago, IL
Zhaofeng Huang
Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, 510080 P.R. China
Ruiqing Wang
Division of Immunology, Beckman Research Institute of the City of Hope; Irell & Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA 91010
Zuoming Sun
Department of Microbiology & Immunology, College of Medicine, University of Illinois at Chicago; Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, CA 91010


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.