NFAT5 induction by the pre-T-cell receptor serves as a selective survival signal in T-lymphocyte development.
Proc Natl Acad Sci U S A
; 110(40): 16091-6, 2013 Oct 01.
Article
em En
| MEDLINE
| ID: mdl-24043824
ABSTRACT
The Rel-like transcription factors nuclear factor kappa B (NF-κB) and the calcineurin-dependent nuclear factor of activated T cells (NFATc) control specific points of thymocyte maturation. Thymocytes also express a distinct member of the Rel family, the calcineurin-independent, osmostress response regulator NFAT5. Here we show that IKKß regulates the expression of NFAT5 in thymocytes, which in turn contributes to the survival of T-cell receptor αß thymocytes and the transition from the ß-selection checkpoint to the double-positive stage in an osmostress-independent manner. NFAT5-deficient thymocytes had normal expression and proximal signaling of the pre-T-cell receptor but exhibited a partial defect in ß-chain allelic exclusion and increased apoptosis. Further analysis showed that NFAT5 regulated the expression of the prosurvival factors A1 and Bcl2 and attenuated the proapoptotic p53/Noxa axis. These findings position NFAT5 as a target of the IKKß/NF-κB pathway in thymocytes and as a downstream effector of the prosurvival role of the pre-T-cell receptor.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
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Transdução de Sinais
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Receptores de Antígenos de Linfócitos T alfa-beta
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Regulação da Expressão Gênica no Desenvolvimento
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Fatores de Transcrição NFATC
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Timócitos
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Espanha