title: Fyn is a redox sensor involved in solar ultraviolet light-induced signal transduction in skin carcinogenesis.
abstract: Solar ultraviolet (UV) light is a major etiological factor in skin carcinogenesis, with solar UV-stimulated signal transduction inducing pathological changes and skin damage. The primary sensor of solar UV-induced cellular signaling has not been identified. We use an experimental system of solar simulated light (SSL) to mimic solar UV and we demonstrate that Fyn is a primary redox sensor involved in SSL-induced signal transduction. Reactive oxygen species (ROS) generated by SSL exposure directly oxidize Cys488 of Fyn, resulting in increased Fyn kinase activity. Fyn oxidation was increased in mouse skin after SSL exposure and Fyn-knockout mice formed larger and more tumors compared with Fyn wild-type mice when exposed to SSL for an extended period of time. Murine embryonic fibroblasts (MEFs) lacking Fyn and cells in which Fyn expression was knocked down were resistant to SSL-induced apoptosis. Furthermore, cells expressing mutant Fyn (C448A) were resistant to SSL-induced apoptosis. These findings suggest that Fyn acts as a regulatory nexus between solar UV, ROS and signal transduction during skin carcinogenesis.
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.|Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: J-E
authors.initials: JE
authors.lastname: Kim
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: E
authors.initials: E
authors.lastname: Roh
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.|China-US Hormel Cancer Institute, Zhenzhou, Henan, China.
authors.forename: M H
authors.initials: MH
authors.lastname: Lee
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Yu
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Kim
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.|Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyeonggi-do, Republic of Korea.|Division of Strategic Food Research, Korea Food Research Institute, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: T-G
authors.initials: TG
authors.lastname: Lim
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.|Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.|Division of Strategic Food Research, Korea Food Research Institute, Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: S K
authors.initials: SK
authors.lastname: Jung
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: C
authors.initials: C
authors.lastname: Peng
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.|College of Pharmacy, The Catholic University of Korea, Bucheon-si, Gyeonggi-do, Republic of Korea.
authors.forename: Y-Y
authors.initials: YY
authors.lastname: Cho
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dickinson
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ, USA.
authors.forename: D
authors.initials: D
authors.lastname: Alberts
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ, USA.
authors.forename: G T
authors.initials: GT
authors.lastname: Bowden
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Einspahr
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Stratton
authors.affiliation: University of Arizona Cancer Center, Tucson, AZ, USA.
authors.forename: C
authors.initials: C
authors.lastname: Curiel-Lewandrowski
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: A M
authors.initials: AM
authors.lastname: Bode
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyeonggi-do, Republic of Korea.
authors.forename: K W
authors.initials: KW
authors.lastname: Lee
authors.affiliation: The Hormel Institute, University of Minnesota, Austin, MN, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D051745:Protein Kinase C-delta / Q000502:physiology; D051076:Proto-Oncogene Proteins c-fyn / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology*; D014466:Ultraviolet Rays
chemical_list: D017382:Reactive Oxygen Species; C497259:Prkcd protein, mouse; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D051745:Protein Kinase C-delta