The beta-catenin--TCF-1 pathway ensures CD4(+)CD8(+) thymocyte survival.


Autoria(s): Ioannidis V.; Beermann F.; Clevers H.; Held W.
Data(s)

2001

Resumo

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.

Identificador

http://serval.unil.ch/?id=serval:BIB_20718

isbn:1529-2908

pmid:11477404

doi:10.1038/90623

isiid:000170230100010

Idioma(s)

en

Fonte

Nature Immunology, vol. 2, no. 8, pp. 691-697

Palavras-Chave #Animals; CD4-Positive T-Lymphocytes/immunology; CD4-Positive T-Lymphocytes/pathology; CD8-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/pathology; Cell Differentiation/immunology; Cell Survival/immunology; Cytoskeletal Proteins/immunology; DNA-Binding Proteins/immunology; Lymphoid Enhancer-Binding Factor 1; Mice; Signal Transduction/immunology; T Cell Transcription Factor 1; Trans-Activators; Transcription Factors/immunology; beta Catenin
Tipo

info:eu-repo/semantics/article

article