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Publication : Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter.

First Author  Jang J Year  2006
Journal  Cell Death Differ Volume  13
Issue  9 Pages  1495-505
PubMed ID  16341126 Mgi Jnum  J:126298
Mgi Id  MGI:3760961 Doi  10.1038/sj.cdd.4401827
Citation  Jang J, et al. (2006) 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
abstractText  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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