UVB-Induced MAPK Signaling
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Pathway Summary
UV radiation is a naturally occurring genotoxic agent and is the primary environmental carcinogen responsible for the development of most skin cancers. UV radiation is composed of UVC (200-280 nm), UVB (280-315 nm) and UVA (315-400 nm). A significant amount of damage produced by solar radiation is caused by UVB, which induces damage to a variety of cellular targets including DNA. In the case of DNA damage, UVB generates oxygen radicals as well as induces cyclobutane pyrimidine dimers and pyrimidine-pyrimidone photo-products. These forms of DNA damage, directly or indirectly, activate a series of signal transduction cascades comprised of serine/threonine kinases and MAPKs.UVB stimulates JNKs, p38 MAPK and ERKs through the EGFR, PKC, or both, leading to varied responses. These responses vary depending on cell type and exposure dose. UVB (100 to 800 J/m2) stimulates a strong activation of JNKs, but weakly stimulates ERKs in a human keratinocyte cell line. In proliferating human epidermal keratinocytes, UVB exposure stimulates phosphorylation of JNKs and p38 MAPK. UVB (4000 J/m2) stimulates the phosphorylation of p38 MAPK and JNKs, but not ERKs. UVB induced MAPKs activate c-Jun and c-Fos (AP-1). Activation of AP-1 does not involve the EGFR. Instead, UVB-induced AP-1 activation involves atypical PKCs. UVB-induced signaling pathways also lead to stabilization and phosphorylation of p53. JNKs mediate UVB-induced p53 phosphorylation at Ser20 while p38 MAPK is involved in UVB-induced phosphorylation of p53 at Ser15. UVB also stimulates BAD phosphorylation at Ser112, which is mediated through MAPK signaling pathways in which JNK1, RSK2, and MSK1 are direct mediators. BAD is a member of the Bcl2 family which is involved in cell survival. UVB can phosphorylate H3 at Ser10 through p38 MAPK. UVB stimulates the phosphorylation of 4EBP1 via mTOR, facilitating its dissociation from eIF4E. This may have a positive effect on cap-dependent initiation of translation. Thus, UVB radiation affects a variety of biological effects.
UVB-Induced MAPK Signaling Genes list
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AKT1AKT serine/threonine kinase 1 BADBCL2 associated agonist of cell death EGFRepidermal growth factor receptor EIF4Eeukaryotic translation initiation factor 4E EIF4EBP1eukaryotic translation initiation factor 4E binding protein 1 FOSFos proto-oncogene, AP-1 transcription factor subunit H3-4H3.4 histone H3C14H3 clustered histone 14 H3C3H3 clustered histone 3 JUNJun proto-oncogene, AP-1 transcription factor subunit MAP2K1mitogen-activated protein kinase kinase 1 MAP2K4mitogen-activated protein kinase kinase 4 MAPK1mitogen-activated protein kinase 1 MAPK10mitogen-activated protein kinase 10 MAPK11mitogen-activated protein kinase 11 MAPK12mitogen-activated protein kinase 12 MAPK13mitogen-activated protein kinase 13 MAPK14mitogen-activated protein kinase 14 MAPK3mitogen-activated protein kinase 3 MAPK8mitogen-activated protein kinase 8 MAPK9mitogen-activated protein kinase 9 MTORmechanistic target of rapamycin kinase PIK3C2Aphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha PIK3C2Bphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta PIK3C2Gphosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 gamma PIK3C3phosphatidylinositol 3-kinase catalytic subunit type 3 PIK3CAphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha PIK3CBphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta PIK3CDphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta PIK3CGphosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma PIK3R1phosphoinositide-3-kinase regulatory subunit 1 PIK3R2phosphoinositide-3-kinase regulatory subunit 2 PIK3R3phosphoinositide-3-kinase regulatory subunit 3 PIK3R4phosphoinositide-3-kinase regulatory subunit 4 PIK3R5phosphoinositide-3-kinase regulatory subunit 5 PIK3R6phosphoinositide-3-kinase regulatory subunit 6 PRKCAprotein kinase C alpha PRKCBprotein kinase C beta PRKCDprotein kinase C delta PRKCEprotein kinase C epsilon PRKCGprotein kinase C gamma PRKCHprotein kinase C eta PRKCIprotein kinase C iota PRKCQprotein kinase C theta PRKCZprotein kinase C zeta PRKD1protein kinase D1 PRKD3protein kinase D3 RPS6KA3ribosomal protein S6 kinase A3 RPS6KA5ribosomal protein S6 kinase A5 RPS6KB1ribosomal protein S6 kinase B1 TP53tumor protein p53
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