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 pro tein. Here we demonstrate that cells respond to pro-oxidant challenge by in ducing ferritin mRNA and protein, and that this response is completely bloc ked by E1A, Concordantly, E1A sensitized cells to the cytotoxic effects of oxidative stress and enhanced the accumulation of reactive oxygen species i n response to prooxidant challenge. These results demonstrate that expressi on of E1A impedes the cellular response to oxidative stress, including the induction of ferritin. (C) 1999 Federation of European Biochemical Societie s.