Adenovirus E1A blocks oxidant-dependent ferritin induction and sensitizes cells to pro-oxidant cytotoxicity.
Ferritin is a protein that oxidizes and sequesters intracellular iron in a mineral core. We have reported that the E1A oncogene selectively represses ferritin H transcription, resulting in reduced levels of the ferritin H protein. Here we demonstrate that cells respond to pro-oxidant challenge by inducing ferritin mRNA and protein, and that this response is completely blocked by E1A. Concordantly, E1A sensitized cells to the cytotoxic effects of oxidative stress and enhanced the accumulation of reactive oxygen species in response to pro-oxidant challenge. These results demonstrate that expression of E1A impedes the cellular response to oxidative stress, including the induction of ferritin.
Orino
K
K
Department of Biochemistry, and the Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Tsuji
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Y
Torti
F M
FM
Torti
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SV
D016475:3T3 Cells; D017500:Adenovirus E1A Proteins / Q000502:physiology*; D000818:Animals; D004249:DNA Damage; D005293:Ferritins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000633:toxicity; D006873:Hydroquinones / Q000633:toxicity; D051379:Mice; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D020033:Protein Isoforms / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection
D017500:Adenovirus E1A Proteins; D006873:Hydroquinones; D020033:Protein Isoforms; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D005293:Ferritins; D006861:Hydrogen Peroxide; C018855:2-tert-butylhydroquinone