Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter.
Cell Death Differ
; 13(9): 1495-505, 2006 Sep.
Article
em En
| MEDLINE
| ID: mdl-16341126
ABSTRACT
One notable phenotypic change during the differentiation of immature thymocytes into either mature CD4 or CD8 single-positive lineages is the acquisition of a resistance to glucocorticoid (GC)-induced apoptosis. We have previously reported that SRG3 is critical in determining the sensitivity for the GC-induced apoptosis in developing thymocytes. We report here that Notch signaling downregulates the transcriptional activation of SRG3 through N-box and/or E-box elements on its promoter. RBP-J represses SRG3 transcription through the N-box motif. On the other hand, Deltex1 competitively inhibits the binding of p300 to E2A/HEB protein bound to the E-box elements and represses the SRG3 promoter activity. Moreover, enforced expression of Deltex1 restored double-positive (DP) thymocyte survival from the GC-induced apoptosis. Our results suggest that Notch signaling confers differentiating DP thymocytes resistance to GCs by regulating the SRG3 expression through Deltex1, and that Deltex1 and SRG3 may play a significant role during DP thymocyte maturation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Linfócitos T
/
Transativadores
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Apoptose
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Proteínas de Ligação a DNA
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Proteína p300 Associada a E1A
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Receptor Notch1
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Glucocorticoides
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Death Differ
Ano de publicação:
2006
Tipo de documento:
Article