title: Notch1 confers thymocytes a resistance to GC-induced apoptosis through Deltex1 by blocking the recruitment of p300 to the SRG3 promoter.
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.
authors.affiliation: Department of Biological Sciences, Institute of Molecular Biology of Genetics, and Center for Functional Cellulomics, Seoul National University, Seoul 151-742, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Jang
authors.forename: Y I
authors.initials: YI
authors.lastname: Choi
authors.forename: J
authors.initials: J
authors.lastname: Choi
authors.forename: K Y
authors.initials: KY
authors.lastname: Lee
authors.forename: H
authors.initials: H
authors.lastname: Chung
authors.forename: S H
authors.initials: SH
authors.lastname: Jeon
authors.forename: R H
authors.initials: RH
authors.lastname: Seong
mesh_terms: D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051881:Receptor, Notch1 / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D050881:E1A-Associated p300 Protein; D005938:Glucocorticoids; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D015514:Oncogene Proteins, Fusion; D051881:Receptor, Notch1; D012097:Repressor Proteins; D015534:Trans-Activators; D044767:Ubiquitin-Protein Ligases; C489626:E2a-Hlf fusion protein, mouse; C497762:Notch1 protein, mouse; C497570:RBPJ protein, human; C489532:Tcf12 protein, mouse; C494361:Ep300 protein, mouse; C104035:Dtx1 protein, mouse