NF-κB/Egr-1/Gadd45 are sequentially activated upon UVB irradiation to mediate epidermal cell death

Thyss, Raphaël; Virolle, Virginie; Imbert, Véronique; Peyron, Jean‐François; Aberdam, Daniel; Virolle, Thierry

doi:10.1038/sj.emboj.7600501

Cited by 143 publications

(137 citation statements)

References 39 publications

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“…In contrast, a very recent study described activation of NF-kB by UVB via an unknown mechanism, which resulted in activation of the transcription factor Egr-1, followed by Egr-1-dependent activation of Gadd 45a/b, which are involved in the nucleotide excision repair. In contrast to the previous observations in which activation of NF-kB by DNA-damaging agents prevented apoptosis, this UVB-triggered cascade contributed to promotion of UVB-induced cell death in epidermal cells (Thyss et al, 2005). This indicates that the impact of NF-kB activation on apoptosis can be heterogenous and thus appears to be a rather complex process.…”

Section: Discussioncontrasting

confidence: 86%

Differential effects of NF-κB on apoptosis induced by DNA-damaging agents: the type of DNA damage determines the final outcome

et al. 2006

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Section: Discussioncontrasting

confidence: 86%

Differential effects of NF-κB on apoptosis induced by DNA-damaging agents: the type of DNA damage determines the final outcome

et al. 2006

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“…NF-kB and EGR-1 have been shown to cooperatively stimulate chemokine gene transcription (49). Moreover, the EGR-1 promoter includes an NF-kB binding motif that is important for the regulation of EGR-1 expression (50). Results from the current study suggested that ATF3 epigenetically regulated EGR-1 expression by recruiting HDAC1 protein (Fig.…”

Section: Discussionmentioning

confidence: 50%

Novel Regulatory Action of Ribosomal Inactivation on Epithelial Nod2-Linked Proinflammatory Signals in Two Convergent ATF3-Associated Pathways

Park

Hun

Choi

et al. 2013

The Journal of Immunology

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In response to excessive nucleotide-binding oligomerization domain–containing protein 2 (Nod2) stimulation caused by mucosal bacterial components, gut epithelia need to activate regulatory machinery to maintain epithelial homeostasis. Activating transcription factor 3 (ATF3) is a representative regulator in the negative feedback loop that modulates TLR-associated inflammatory responses. In the current study, the regulatory effects of ribosomal stress-induced ATF3 on Nod2-stimulated proinflammatory signals were assessed. Ribosomal inactivation caused persistent ATF3 expression that in turn suppressed proinflammatory chemokine production facilitated by Nod2. Decreased chemokine production was due to attenuation of Nod2-activated NF-κB and early growth response protein 1 (EGR-1) signals by ATF3. However, the underlying molecular mechanisms involve two convergent regulatory pathways. Although ATF3 induced by ribosomal inactivation regulated Nod2-induced EGR-1 expression epigenetically through the recruitment of histone deacetylase 1, NF-κB regulation was associated with posttranscriptional regulation by ATF3 rather than epigenetic modification. ATF3 induced by ribosomal inactivation led to the destabilization of p65 mRNA caused by nuclear entrapment of transcript-stabilizing human Ag R protein via direct interaction with ATF3. These findings demonstrate that ribosomal stress-induced ATF3 is a critical regulator in the convergent pathways between EGR-1 and NF-κB, which contributes to the suppression of Nod2-activated proinflammatory gene expression.

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“…7A) [33,34]. PGE 2 treatment of HCA-7 cells transiently transfected with pEgr-1A construct resulted in significant increase in luciferase activity compared to the vehicle-treated cells (Fig.…”

Section: Creb Phosphorylation By Erk Is Attenuated By L-161982mentioning

confidence: 85%

The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells

Cherukuri

Chen

Goulet

et al. 2007

Experimental Cell Research

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Accumulating evidence indicates that elevated levels of prostaglandin E 2 (PGE 2 ) can increase intestinal epithelial cell proliferation, and thus play a role in colorectal tumorigenesis. PGE 2 exerts its effects through four G-protein coupled PGE receptor (EP) subtypes, named the EP1, EP2, EP3, and EP4. Increased phosphorylation of extracellular regulated kinases (ERK1/2) is required for PGE 2 to stimulate cell proliferation of human colon cancer cells. However, the EP receptor(s) that are involved in this process remain unknown. We provide evidence that L-161,982, a selective EP4 receptor antagonist, completely blocks PGE 2 -induced ERK phosphorylation and cell proliferation of HCA-7 cells. In order to identify downstream target genes of ERK1/2 signaling, we found that PGE 2 induces expression of early growth response gene-1 (EGR-1) downstream of ERK1/2 and regulates its expression at the level of transcription. PGE 2 treatment induces phosphorylation of cyclic AMP response element binding protein (CREB) at Ser133 residue and CRE-mediated luciferase activity in HCA-7 cells. Studies with dominant negative CREB mutant (ACREB) provide clear evidence for the involvement of CREB in PGE 2 driven egr-1 transcription in HCA-7 cells. In conclusion, this study reveals that egr-1 is a target gene of PGE 2 in HCA-7 cells and is regulated via the newly identified EP4/ERK/CREB pathway. Finally our results support the notion that antagonizing EP4 receptors may provide a novel therapeutic approach to the treatment of colon cancer.

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NF-κB/Egr-1/Gadd45 are sequentially activated upon UVB irradiation to mediate epidermal cell death

Cited by 143 publications

References 39 publications

Differential effects of NF-κB on apoptosis induced by DNA-damaging agents: the type of DNA damage determines the final outcome

Differential effects of NF-κB on apoptosis induced by DNA-damaging agents: the type of DNA damage determines the final outcome

Novel Regulatory Action of Ribosomal Inactivation on Epithelial Nod2-Linked Proinflammatory Signals in Two Convergent ATF3-Associated Pathways

The EP4 receptor antagonist, L-161,982, blocks prostaglandin E2-induced signal transduction and cell proliferation in HCA-7 colon cancer cells

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