Dexamethasone-induced Gene 2 (dig2) Is a Novel Pro-survival Stress Gene Induced Rapidly by Diverse Apoptotic Signals
Open accessAbstract
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.
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Three genes overlapped between the microglial and astrocyte factors that were not part of consensus mouse gene lists (UBC, DDIT4 and HSPB1), and these are part of cellular stress and damage response machinery.
“Finally, there were three genes that overlapped between the microglial and astrocyte factors that were not a part of consensus mouse gene lists (UBC, DDIT4 and HSPB1), but which unsurprisingly are also part of cellular stress and damage response machinery52–55.”
From Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain (2022) · cites this paper as [53]
The Discussion identifies dig2 as a stress-response gene induced by diverse cellular stressors, supporting the stress-response characterization of the gene studied here. Our copy does not identify dig2 as DDIT4, so it does not establish that this paper supports the claim specifically about DDIT4. The microglial–astrocyte overlap is the citing authors’ finding, not a finding attributed to this source. (LLM, conf=0.78)
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- Authors
- Wang, Z., Malone, M. H., Thomenius, M. J., Zhong, F., Xu, F., & Distelhorst, C. W.
- Affiliations
- University Hospitals of Cleveland (US)
- Corresponding author
- Distelhorst, Clark W.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2003-07
- Volume
- 278
- Issue
- 29
- Pages
- 27053-27058
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2077001140
- Cited by
- 144
- References
- 16
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 8 · 2022: 7 · 2021: 9 · 2020: 3 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 9 · 2013: 9 · 2012: 3
- FWCI
- 2.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Case Western Reserve University (P30 CA43703)
- National Institutes of Health (5r01ca079806-05, CA43703)
- National Cancer Institute (T32CA073515, R01CA042755, P30 CA53703, R01 CA79806, P30CA043703, T32CA059366)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- glucocorticoid-induced apoptosis, glucocorticoid receptor, thymocytes, T-cell lymphoma, apoptosis, etoposide, thapsigargin, tunicamycin, heat shock, gene induction, RU486
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Cell Survival, Cloning, Molecular, Dexamethasone, DNA-Binding Proteins, Etoposide, Female, Mice, Inbred C57BL, Molecular Sequence Data, RNA, Messenger, T-Lymphocytes, Transcription Factors, Tumor Cells, Cultured, Apoptosis, DNA, Complementary, Expressed Sequence Tags, Oligonucleotide Array Sequence Analysis, Adaptor Proteins, Signal Transducing, Mice, In Vitro Techniques
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