title: UVA, UVB and UVC induce differential response signaling pathways converged on the eIF2α phosphorylation.
abstract: It is clear that solar UV irradiation is a crucial environmental factor resulting in skin diseases partially through activation of cell signaling toward altered gene expression and reprogrammed protein translation. Such a key translational control mechanism is executed by the eukaryotic initiation factor 2α subunit (eIF2α) and the downstream events provoked by phosphorylation of eIF2α at Ser(51) are clearly understood, but the upstream signaling mechanisms on the eIF2α-Ser(51) phosphorylation responses to different types of UV irradiations, namely UVA, UVB and UVC, are still not well elucidated. Herein, our evidence reveals that UVA, UVB and UVC all induce a dose- and time-dependent phosphorylation of eIF2α-Ser(51) through distinct signaling mechanisms. UVA-induced eIF2α phosphorylation occurs through MAPKs, including ERKs, JNKs and p38 kinase, and phosphatidylinositol (PI)-3 kinase. By contrast, UVB-induced eIF2α phosphorylation is through JNKs and p38 kinase, but not ERKs or PI-3 kinase, whereas UVC-stimulated response to eIF2α phosphorylation is via JNKs alone. Furthermore, we have revealed that ATM is involved in induction of the intracellular responses to UVA and UVB, rather than UVC. These findings demonstrate that wavelength-specific UV irradiations activate differential response signaling pathways converged on the eIF2α phosphorylation. Importantly, we also show evidence that a direct eIF2α kinase PKR is activated though phosphorylation by either RSK1 or MSK1, two downstream kinases of MAPKs/PI-3 kinase-mediated signaling pathways.
authors.affiliation: The Base of 111 Project for Biomechanics & Tissue Repair Engineering, College of Medical Bioengineering, University of Chongqing, Shapingba District, Chongqing, China.
authors.forename: Julia Li
authors.initials: JL
authors.lastname: Zhong
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Fenglin
authors.initials: F
authors.lastname: Lü
authors.forename: Han
authors.initials: H
authors.lastname: Xiao
authors.forename: Ruoqi
authors.initials: R
authors.lastname: Xu
authors.forename: Lijuan
authors.initials: L
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Yiguo
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000528:radiation effects; D039642:Eukaryotic Initiation Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000528:radiation effects; D010957:Plasmids; D012694:Serine / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects*; D014162:Transfection; D014466:Ultraviolet Rays / Q000009:adverse effects; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D039642:Eukaryotic Initiation Factors; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D012694:Serine; D019892:eIF-2 Kinase