title: Protein kinase Cepsilon inhibits UVR-induced expression of FADD, an adaptor protein, linked to both Fas- and TNFR1-mediated apoptosis.
abstract: Protein kinase C (PKC)epsilon overexpression in FVB/N transgenic mice sensitized skin to UVR-induced development of squamous cell carcinomas and suppressed formation of sunburn cells, which are DNA-damaged keratinocytes undergoing apoptosis. Here, we elucidated the mechanisms associated with the inhibition of UVR-induced appearance of sunburn cells in PKCepsilon transgenic mice. We found that the inhibition of UVR-induced sunburn cell formation in PKCepsilon transgenic mice may be the result of the inhibition of the expression of Fas, Fas ligand, and the mammalian death adaptor protein termed Fas-associated with death domain (FADD). The adaptor protein FADD is the key component of the death-inducing signaling complex of both Fas and tumor necrosis factor receptor 1. A decreased expression of epidermal FADD was observed after a single UVR exposure. However, a complete loss of FADD expression was found after four (Monday, Wednesday, Friday, and Monday) repeated UVR exposures. FADD transmits apoptotic signals from death receptors to the downstream initiator caspase-8 and connects to the mitochondrial intrinsic apoptotic signal transduction pathway by the cleavage of Bid, a Bcl-2 family member. PKCepsilon-mediated loss of FADD expression inhibited UVR signals to the activation of both extrinsic and intrinsic apoptotic pathways.
authors.affiliation: Department of Human Oncology, Medical School, University of Wisconsin, Madison, Wisconsin 53792, USA.
authors.forename: Moammir Hasan
authors.initials: MH
authors.lastname: Aziz
authors.forename: Kaitlin Elizabeth
authors.initials: KE
authors.lastname: Sundling
authors.forename: Nancy Ellen
authors.initials: NE
authors.lastname: Dreckschmidt
authors.forename: Ajit Kumar
authors.initials: AK
authors.lastname: Verma
mesh_terms: D000818:Animals; D017209:Apoptosis; D051023:BH3 Interacting Domain Death Agonist Protein / Q000037:antagonists & inhibitors; D053200:Fas-Associated Death Domain Protein / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000502:physiology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014466:Ultraviolet Rays; D019014:fas Receptor / Q000502:physiology*
chemical_list: D051023:BH3 Interacting Domain Death Agonist Protein; C494815:Bid protein, mouse; C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; C506236:Tnfrsf1a protein, mouse; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D011065:Poly(ADP-ribose) Polymerases; D051744:Protein Kinase C-epsilon