The Role of JNK and p38 MAPK Activities in UVA-Induced Signaling Pathways Leading to AP-1 Activation and c-Fos Expression

Silvers, Amy L.; Bachelor, Michael; Bowden, G. Timothy

doi:10.1016/s1476-5586(03)80025-8

Cited by 109 publications

(104 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pretreatment with EPA inhibited UV-induced AP-1 DNA binding activity in a dose-dependent manner at 10 h after UV (Fig. 3B) (23)(24)(25). UV radiation rapidly induced the phosphorylation of Elk-1, and pretreatment with EPA dramatically inhibited UV-induced Elk-1 phosphorylation in a dose-dependent manner (Fig.…”

Section: Epa Inhibited Uv-induced Ap-1 Activation C-jun Phosphorylatmentioning

confidence: 94%

Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts

Kim

Shin

Park

et al. 2005

Journal of Lipid Research

110

View full text Add to dashboard Cite

show abstract

Section: Epa Inhibited Uv-induced Ap-1 Activation C-jun Phosphorylatmentioning

confidence: 94%

Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts

Kim

Shin

Park

et al. 2005

Journal of Lipid Research

110

View full text Add to dashboard Cite

show abstract

“…Extensive investigation of the response of mammalian cells to UV light has shown that exposure to UV light results in the rapid activation of a group of enzymes known as stress-activated protein kinases (SAPKs) 1 (1,2) and the induction of expression of a set of immediate early genes (ergs) (3)(4)(5)(6), which in turn participate in the cellular responses to this type of environmental stress.…”

mentioning

confidence: 99%

Phosphorylation of c-Fos by Members of the p38 MAPK Family

Tanos

Marinissen

Leskow

et al. 2005

Journal of Biological Chemistry

181

141

View full text Add to dashboard Cite

Exposure to sources of UV radiation, such as sunlight, induces a number of cellular alterations that are highly dependent on its ability to affect gene expression. Among them, the rapid activation of genes coding for two subfamilies of proto-oncoproteins, Fos and Jun, which constitute the AP-1 transcription factor, plays a key role in the subsequent regulation of expression of genes involved in DNA repair, cell proliferation, cell cycle arrest, death by apoptosis, and tissue and extracellular matrix remodeling proteases. Besides being regulated at the transcriptional level, Jun and Fos transcriptional activities are also regulated by phosphorylation as a result of the activation of intracellular signaling cascades. In this regard, the phosphorylation of c-Jun by UV-induced JNK has been readily documented, whereas a role for Fos proteins in UV-mediated responses and the identification of Fosactivating kinases has remained elusive. Here we identify p38 MAPKs as proteins that can associate with c-Fos and phosphorylate its transactivation domain both in vitro and in vivo. This phosphorylation is transduced into changes in its transcriptional ability as p38-activated c-Fos enhances AP1-driven gene expression. Our findings indicate that as a consequence of the activation of stress pathways induced by UV light, endogenous c-Fos becomes a substrate of p38 MAPKs and, for the first time, provide evidence that support a critical role for p38 MAPKs in mediating stress-induced c-Fos phosphorylation and gene transcription activation. Using a specific pharmacological inhibitor for p38␣ and -␤, we found that most likely these two isoforms mediate UV-induced c-Fos phosphorylation in vivo. Thus, these newly described pathways act concomitantly with the activation of c-Jun by JNK/ MAPKs, thereby contributing to the complexity of AP1-driven gene transcription regulation.Repeated and prolonged exposure to sunlight and hence to UV radiation causes skin damage that may induce alterations in the DNA and ultimately evolve into skin cancer. Extensive investigation of the response of mammalian cells to UV light has shown that exposure to UV light results in the rapid activation of a group of enzymes known as stress-activated protein kinases (SAPKs) 1 (1, 2) and the induction of expression of a set of immediate early genes (ergs) (3-6), which in turn participate in the cellular responses to this type of environmental stress.SAPKs is the common denomination for a subgroup of highly homologous proteins, JNKs and p38s, that belong to a superfamily of serine-threonine kinases known as mitogen-activated protein kinases (MAPKs) (7-10). These kinases play an essential role in the transduction of environmental stimuli to the nucleus, as they are capable of regulating the expression of genes involved in a variety of cellular processes, including cell proliferation, differentiation, programmed cell death, and neoplastic transformation (11-13). MAPKs have been classified into at least six subfamilies, among which the Erk/MAPKs (Erk1 and -2), JNKs (JN...

show abstract

“…Low JNK activity in cultured keratinocytes can be further activated e.g. by UV light (21)(22)(23)(24). Active JNK is associated with keratinocyte proliferation (25) but does not play a role in keratinocyte motility (26 -29).…”

mentioning

confidence: 99%

Inhibition of JNK Promotes Differentiation of Epidermal Keratinocytes

Gazel

Banno

Walsh

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

In inflamed tissue, normal signal transduction pathways are altered by extracellular signals. For example, the JNK pathway is activated in psoriatic skin, which makes it an attractive target for treatment. To define comprehensively the JNK-regulated genes in human epidermal keratinocytes, we compared the transcriptional profiles of control and JNK inhibitor-treated keratinocytes, using DNA microarrays. We identified the differentially expressed genes 1, 4, 24, and 48 h after the treatment with SP600125. Surprisingly, the inhibition of JNK in keratinocyte cultures in vitro induces virtually all aspects of epidermal differentiation in vivo: transcription of cornification markers, inhibition of motility, withdrawal from the cell cycle, stratification, and even production of cornified envelopes. The inhibition of JNK also induces the production of enzymes of lipid and steroid metabolism, proteins of the diacylglycerol and inositol phosphate pathways, mitochondrial proteins, histones, and DNA repair enzymes, which have not been associated with differentiation previously. Simultaneously, basal cell markers, including integrins, hemidesmosome and extracellular matrix components, are suppressed. Promoter analysis of regulated genes finds that the binding sites for the forkhead family of transcription factors are over-represented in the SP600125-induced genes and c-Fos sites in the suppressed genes. The JNK-induced proliferation appears to be secondary to inhibition of differentiation. The results indicate that the inhibition of JNK in epidermal keratinocytes is sufficient to initiate their differentiation program and suggest that augmenting JNK activity could be used to delay cornification and enhance wound healing, whereas attenuating it could be a differentiation therapy-based approach for treating psoriasis.

show abstract

The Role of JNK and p38 MAPK Activities in UVA-Induced Signaling Pathways Leading to AP-1 Activation and c-Fos Expression

Cited by 109 publications

References 57 publications

Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts

Eicosapentaenoic acid inhibits UV-induced MMP-1 expression in human dermal fibroblasts

Phosphorylation of c-Fos by Members of the p38 MAPK Family

Inhibition of JNK Promotes Differentiation of Epidermal Keratinocytes

Contact Info

Product

Resources

About