Stabilized beta-catenin extends thymocyte survival by up-regulating Bcl-xL.
CD4+CD8+ double-positive (DP) thymocytes, which are extremely sensitive to apoptosis, specifically up-regulate Bcl-xL to extend their lifespan. Deletion of the Bcl-xL gene leads to premature apoptosis of the thymocytes. In this study, we show that stabilization of beta-catenin, a critical coactivator for T cell factor (TCF), enhances DP thymocyte survival via up-regulating Bcl-xL. Spontaneous or glucocorticoid-induced thymocyte apoptosis was associated with reduced levels of beta-catenin and Bcl-xL. Transgenic expression of a stabilized beta-catenin protected DP thymocytes from both spontaneous and glucocorticoid-induced apoptosis, resulting in significantly increased thymic cellularity. Compared with the wild-type mice, both protein and transcript levels of Bcl-xL were significantly increased in thymocytes of beta-catenin transgenic mice. In addition, TCF-1 as well as beta-catenin were able to stimulate transcriptional activity of the reporter driven by a Bcl-xL promoter. beta-Catenin/TCF is thus able to act as a signal to up-regulate Bcl-xL levels in DP thymocytes, resulting in their enhanced survival.
Xie
Huimin
H
Department of Microbiology and Immunology, College of Medicine, University of Illinois, Chicago, IL 60612, USA.
Huang
Zhaofeng
Z
Sadim
Maureen S
MS
Sun
Zuoming
Z
D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D005938:Glucocorticoids / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D051822:T Cell Transcription Factor 1 / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology*; D014158:Transcription, Genetic; D015854:Up-Regulation; D051020:bcl-X Protein / Q000032:analysis / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics / Q000502:physiology*
C494812:Bcl2l1 protein, mouse; D005938:Glucocorticoids; D012333:RNA, Messenger; D051822:T Cell Transcription Factor 1; D051020:bcl-X Protein; D051176:beta Catenin