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Critical Reviews™ in Immunology

ISSN for PRINT: 1040-8401

Institutional price:	$831.00
Issues per year:	6

Best Paper Award Selection - Editorial Board Site

2006, Volume26

111 pages

Issue price - $142.00

Regulation of Thymocyte Survival by Transcriptional Coactivators

Huimin Xie
Department of Microbiology & Immunology, College of Medicine, University of Illinois, Chicago, IL

Zhaofeng Huang
Department of Microbiology & Immunology, College of Medicine, University of Illinois, Chicago, IL

Ruiqing Wang
Department of Microbiology & Immunology, College of Medicine, University of Illinois, Chicago, IL

Zuoming Sun
Department of Microbiology & Immunology, College of Medicine, University of Illinois at Chicago, 835 S. Wolcott (M/C790), Chicago, IL

ABSTRACT

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-x_L, a critical survival factor for CD4⁺CD8⁺ double-positive thymocytes. However, TCF-1 and RORγt by themselves are not sufficient to stimulate Bcl-x_L 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-x_L expression. Thus, transcriptional coactivators are a substantial component of the transcriptional machinery to regulate thymocye survival, ensuring the completion of T-cell development.