The beta-catenin--TCF-1 pathway ensures CD4(+)CD8(+) thymocyte survival.
The association of trans-acting T cell factors (TCFs) or lymphoid enhancer factor 1 (LEF-1) with their coactivator beta-catenin mediates transient transcriptional responses to extracellular Wnt signals. We show here that T cell maturation depends on the presence of the beta-catenin--binding domain in TCF-1. This domain is necessary to mediate the survival of immature CD4(+)CD8(+) double-positive (DP) thymocytes. Accelerated spontaneous thymocyte death in the absence of TCF-1 correlates with aberrantly low expression of the anti-apoptotic protein Bcl-x(L). Increasing anti-apoptotic effectors in thymocytes by the use of a Bcl-2 transgene rescued TCF-1-deficient DP thymocytes from apoptosis. Thus, TCF-1, upon association with beta-catenin, transiently ensures the survival of immature T cells, which enables them to generate and edit T cell receptor (TCR) alpha chains and attempt TCR-mediated positive selection.
Ioannidis
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V
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, 155 Ch. des Boveresses, 1066 Epalinges, Switzerland.
Beermann
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F
Clevers
H
H
Held
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W
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D003598:Cytoskeletal Proteins / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000276:immunology*; D051538:Hepatocyte Nuclear Factor 1-alpha; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D015398:Signal Transduction / Q000276:immunology; D051822:T Cell Transcription Factor 1; D015534:Trans-Activators; D014157:Transcription Factors / Q000276:immunology*; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D051822:T Cell Transcription Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin