2014
DOI: 10.1074/jbc.m113.490920
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Modulation of Nuclear Factor E2-related Factor-2 (Nrf2) Activation by the Stress Response Gene Immediate Early Response-3 (IER3) in Colonic Epithelial Cells

Abstract: Background: Nrf2 has a dual role in tumorigenesis. Results: Nrf2 activation in colonic epithelial cells is controlled by the stress response gene IER3. Loss of IER3 expression causes enhanced Nrf2 activity, thereby conferring ROS protection and apoptosis resistance. Conclusion: By regulating Nrf2-dependent cytoprotection, IER3 exerts tumor suppressive activity. Significance: Loss of control by IER3 favors the protumorigenic action of Nrf2.

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Cited by 49 publications
(24 citation statements)
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“…IER3-deficient NCM460 cells exhibited reduced reactive oxygen species levels, indicating increased antioxidative protection [50]. In our study, IER3 was down regulated in the VE group suggesting an increase in antioxidative protection.…”
Section: Discussionmentioning
confidence: 47%
“…IER3-deficient NCM460 cells exhibited reduced reactive oxygen species levels, indicating increased antioxidative protection [50]. In our study, IER3 was down regulated in the VE group suggesting an increase in antioxidative protection.…”
Section: Discussionmentioning
confidence: 47%
“…Furthermore, a short pilot study was done on 12 children treated with IFN leading to small but significant increase of FXN expression and enhancement of the Friedreich Ataxia Rating Scale after 12 weeks of treatment [49]. Interestingly, IER3, another interferon-stimulated genes, found to be down-regulated in our gene list, has been shown to modulate Nrf2 expression in stress response [50]. Nrf2, anti-oxidative transcription factor, has been reported to be impaired in FRDA patient cells thus leading to cell hypersensitivity and oxidative insults [51].…”
Section: Accepted Manuscriptmentioning
confidence: 94%
“…Another immune modulator is the immediate early response protein IER3, being associated with inflammatory stress and inflammatory diseases. 45,46 In addition, it is conserved in rodents and humans, where it enhances apoptosis upon DNA damage, p53 activation or diverse stimuli such as TNFα, TRAIL or irradiation.…”
Section: Discussionmentioning
confidence: 99%