Protein kinase Cepsilon inhibits UVR-induced expression of FADD, an adaptor protein, linked to both Fas- and TNFR1-mediated apoptosis.
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.
Aziz
Moammir Hasan
MH
Department of Human Oncology, Medical School, University of Wisconsin, Madison, Wisconsin 53792, USA.
Sundling
Kaitlin Elizabeth
KE
Dreckschmidt
Nancy Ellen
NE
Verma
Ajit Kumar
AK
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*
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