E7 viral oncoprotein negatively influences the transcriptional activity of the L1Md retrotransposon promoter under conditions of cellular stress.

Abstract

Retrotransposons are mobile elements that modify the eukaryotic genome mostly through insertions, deletions, and inversions that potentially lead to disease. Activation of retroelements is observed under conditions of stress and in cancer. We previously identified a mouse L1Md retrotransposon as a redox-regulated gene and characterized an antioxidant response element (ARE) within its 5′ promoter region that confers carcinogen sensitivity. E7 is a viral oncoprotein that associates with basal transcription factors including TATA-binding protein (TBP) and AP1 family members including c-Jun, JunB, JunD, and c-Fos. AP1 proteins are activated in response to oxidative stress and bind AREs. Through transient transcription assays in HeLa cells we measured the effect of forced E7 expression on L1MdA promoter activity following challenge with the carcinogen benzo(a)pyrene. E7 ablated the response of the reporter gene to carcinogen treatment, but did not interfere with basal transcriptional activity. We suggest that E7 associates with transcription factors required for proper assembly of the transcription macromolecular complex that assembles on the ARE or its vicinity. This is the first report showing that E7 might be involved in the regulation of retrotransposon transcriptional activity via the ARE. (This work was supported by ES Grant 04849 to KSR).