Regulation of thymocyte survival by transcriptional coactivators.
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 ROR gamma t, are required to upregulate the levels of Bcl-xL, a critical survival factor for CD4+CD8+ double-positive thymocytes. However, TCF-1 and ROR gamma t by themselves are not sufficient to stimulate Bcl-xL expression. Transcriptional coactivator beta-catenin recruited by TCF-1, and steroid receptor coactivators (SRCs) recruited by ROR gamma t, 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.
Xie
Huimin
H
Department of Microbiology & Immunology, College of Medicine, University of Illinois, Chicago, IL 60612, USA.
Huang
Zhaofeng
Z
Wang
Ruiqing
R
Sun
Zuoming
Z
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D018448:Models, Immunological; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D051822:T Cell Transcription Factor 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development* / Q000276:immunology; D015533:Transcriptional Activation; D051020:bcl-X Protein / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D051176:beta Catenin / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D051958:Nuclear Receptor Coactivator 2; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; D051822:T Cell Transcription Factor 1; D051020:bcl-X Protein; D051176:beta Catenin