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Notch1 confers a resistance to glucocorticoid-induced apoptosis on developing thymocytes by down-regulating SRG3 expression
- Source :
- Proceedings of the National Academy of Sciences of the United States of America. 98(18)
- Publication Year :
- 2001
-
Abstract
- We previously have reported that SRG3 is required for glucocorticoid (GC)-induced apoptosis in the S49.1 thymoma cell line. Activation of Notch1 was shown to induce GC resistance in thymocytes. However, the specific downstream target of Notch1 that confers GC resistance on thymocytes is currently unknown. We found that the expression level of SRG3 was critical in determining GC sensitivity in developing thymocytes. The expression of SRG3 also was down-regulated by the activated form of Notch1 (NotchIC). The promoter activity of the SRG3 gene also was down-regulated by NotchIC. Expression of transgenic SRG3 resulted in the restoration of GC sensitivity in thymocytes expressing transgenic Notch1. These results suggest that SRG3 is the downstream target of Notch1 in regulating GC sensitivity of thymocytes.
- Subjects :
- Male
Cellular differentiation
Transgene
T-Lymphocytes
Drug Resistance
Repressor
Down-Regulation
Apoptosis
Mice, Transgenic
Receptors, Cell Surface
Biology
Dexamethasone
Cell Line
Mice
Downregulation and upregulation
hemic and lymphatic diseases
medicine
Animals
RNA, Messenger
Receptor, Notch1
Promoter Regions, Genetic
Transcription factor
Glucocorticoids
DNA Primers
Multidisciplinary
Base Sequence
Membrane Proteins
Cell Differentiation
Biological Sciences
Molecular biology
Mice, Inbred C57BL
Repressor Proteins
Cell culture
embryonic structures
cardiovascular system
Trans-Activators
Female
sense organs
biological phenomena, cell phenomena, and immunity
Glucocorticoid
medicine.drug
Transcription Factors
Subjects
Details
- ISSN :
- 00278424
- Volume :
- 98
- Issue :
- 18
- Database :
- OpenAIRE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Accession number :
- edsair.doi.dedup.....1ab86d88b1dc89c84f167ead17f89578