The Ets-1 transcription factor is required for complete pre-T cell receptor function and allelic exclusion at the T cell receptor beta locus.
Proc Natl Acad Sci U S A
; 101(44): 15712-7, 2004 Nov 02.
Article
em En
| MEDLINE
| ID: mdl-15496469
ABSTRACT
The pre-T cell receptor (TCR) functions as a critical checkpoint during alphabeta T cell development. Signaling through the pre-TCR controls the differentiation of immature CD4(-)CD8(-)CD25(+)CD44(-) [double-negative (DN)3] thymocytes into CD4(+)CD8(+) double-positive (DP) cells through the CD4(-)CD8(-)CD25(-)CD44(-)(DN4) stage. In addition, pre-TCR activity triggers expansion and survival of thymocytes and inhibits TCRbeta gene rearrangement through a process referred to as allelic exclusion. Whereas many proteins involved in the pre-TCR transduction cascade have been identified, little is known about the nuclear factors associated with receptor function. Here, we use gene targeting to inactivate the Ets-1 transcription factor in mice and analyze pre-TCR function in developing Ets-1-deficient (Ets-1(-/-)) thymocytes. We find that inactivation of Ets-1 impairs the development of DN3 into DP thymocytes and induces an elevated rate of cell death in the DN4 subset. This defect appears specific to the alphabeta lineage because gammadelta T cells maturate efficiently. Finally, the percentage of thymocytes coexpressing two different TCRbeta chains is increased in the Ets-1(-/-) background and, in contrast with wild type, forced activation of pre-TCR signaling does not block endogenous TCRbeta gene rearrangement. These data identify Ets-1 as a critical transcription factor for pre-TCR functioning and for allelic exclusion at the TCRbeta locus.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Proteínas Proto-Oncogênicas
/
Receptores de Antígenos de Linfócitos T alfa-beta
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article