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Dexamethasone-induced gene 2 (dig2) is a novel pro-survival stress gene induced rapidly by diverse apoptotic signals.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2003 Jul 18; Vol. 278 (29), pp. 27053-8. Date of Electronic Publication: 2003 May 07. - Publication Year :
- 2003
-
Abstract
- Glucocorticoid hormones induce apoptosis in lymphoid cells. This process requires de novo RNA/protein synthesis. Here we report the identification and cloning of a novel dexamethasone-induced gene designated dig2. Using Affymetrix oligonucleotide microarray analysis of approximately 10,000 genes and expressed sequence tags, we found that the expression of dig2 mRNA is significantly induced not only in the murine T cell lymphoma lines S49.A2 and WEHI7.2 but also in normal mouse thymocytes following dexamethasone treatment. This result was confirmed by Northern blot analysis. The induction of dig2 mRNA by dexamethasone appears to be mediated through the glucocorticoid receptor as it is blocked in the presence of RU486, a glucocorticoid receptor antagonist. Furthermore, we demonstrated that dig2 is a novel stress response gene, as its mRNA is induced in response to a variety of cellular stressors including thapsigargin, tunicamycin, and heat shock. In addition, the levels of dig2 mRNA were up-regulated after treatment with the apoptosis-inducing chemotherapeutic drug etoposide. Though the function of dig2 is unknown, dig2 appears to have a pro-survival function, as overexpression of dig2 reduces the sensitivity of WEHI7.2 cells to dexamethasone-induced apoptosis.
- Subjects :
- Adaptor Proteins, Signal Transducing
Amino Acid Sequence
Animals
Apoptosis drug effects
Base Sequence
Cell Survival drug effects
Cell Survival genetics
Cloning, Molecular
DNA, Complementary genetics
Dexamethasone pharmacology
Etoposide pharmacology
Expressed Sequence Tags
Female
In Vitro Techniques
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Oligonucleotide Array Sequence Analysis
RNA, Messenger biosynthesis
RNA, Messenger genetics
T-Lymphocytes cytology
T-Lymphocytes drug effects
T-Lymphocytes metabolism
Tumor Cells, Cultured
Apoptosis genetics
DNA-Binding Proteins genetics
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 278
- Issue :
- 29
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12736248
- Full Text :
- https://doi.org/10.1074/jbc.M303723200