Cited by 96Autophagy in Disease and TherapyCell death mechanisms and regulationPI3K/AKT/mTOR signaling in cancer

The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.

Glucocorticoid Elevation of Dexamethasone-induced Gene 2 (Dig2/RTP801/REDD1) Protein Mediates Autophagy in Lymphocytes

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Abstract

Glucocorticoid hormones, including dexamethasone, induce apoptosis in lymphocytes and consequently are used clinically as chemotherapeutic agents in many hematologic malignancies. Dexamethasone also induces autophagy in lymphocytes, although the mechanism is not fully elucidated. Through gene expression analysis, we found that dexamethasone induces the expression of a gene encoding a stress response protein variously referred to as Dig2, RTP801, or REDD1. This protein is reported to inhibit mammalian target of rapamycin (mTOR) signaling. Because autophagy is one outcome of mTOR inhibition, we investigated the hypothesis that Dig2/RTP801/REDD1 elevation contributes to autophagy induction in dexamethasone-treated lymphocytes. In support of this hypothesis, RNAi-mediated suppression of Dig2/RTP801/REDD1 reduces mTOR inhibition and autophagy in glucocorticoid-treated lymphocytes. We observed similar results in Dig2/Rtp801/Redd1 knock-out murine thymocytes treated with dexamethasone. Dig2/RTP801/REDD1 knockdown also leads to increased levels of dexamethasone-induced cell death, suggesting that Dig2/RTP801/REDD1-mediated autophagy promotes cell survival. Collectively, these findings demonstrate for the first time that elevation of Dig2/RTP801/REDD1 contributes to the induction of autophagy.

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Crossref · 10.1074/jbc.m111.245423

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  • Glucocorticoids reduce circulating T cells by enhancing their migration to bone marrow and secondary lymphoid organs and trigger T cell apoptosis through up-regulation of BIM.

    “In contrast to neutrophils, GCs reduce the levels of circulating T cells by enhancing their migration back to the bone-marrow and secondary lymphoid organs (47, 48). GCs also trigger T cells apoptosis, notably through the up-regulation of BIM (49, 50).”

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Metadata

Authors
Molitoris, J. K., McColl, K. S., Swerdlow, S., Matsuyama, M., Lam, M., Finkel, T. H., Matsuyama, S., & Distelhorst, C. W.
Affiliations
  • University Hospitals of Cleveland (US)
  • University of Pennsylvania (US)
Corresponding author
Distelhorst, Clark W.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2011-08
Volume
286
Issue
34
Pages
30181-30189
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1995383659
Cited by
96
References
53
Citations by year
2026: 4 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 12 · 2017: 6 · 2016: 8 · 2015: 6 · 2014: 12 · 2013: 9 · 2012: 4
FWCI
6.27
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (GM007250)
  • National Institute on Aging (R01AG031903)
  • National Heart, Lung, and Blood Institute (T32HL007147)
  • National Cancer Institute (CA85804, R01 CA42755, R01CA042755, R01CA085804)
  • National Institute of General Medical Sciences (T32GM007250)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
dexamethasone, autophagy, lymphocytes, glucocorticoids, mTOR inhibition, stress proteins, apoptosis, thymocytes, cell survival, hematologic malignancies
MeSH terms
Animals, Anti-Inflammatory Agents, Autophagy, Cell Line, Cell Survival, Dexamethasone, Lymphocytes, Transcription Factors, Mice, Knockout, Mice, TOR Serine-Threonine Kinases

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