title: Human papillomavirus E7 enhances hypoxia-inducible factor 1-mediated transcription by inhibiting binding of histone deacetylases.
abstract: Infection by human papillomaviruses (HPV) leads to the formation of benign lesions, warts, and in some cases, cervical cancer. The formation of these lesions is dependent upon increased expression of proangiogenic factors. Angiogenesis is linked to tissue hypoxia through the activity of the oxygen-sensitive hypoxia-inducible factor 1α (HIF-1α). Our studies indicate that the HPV E7 protein enhances HIF-1 transcriptional activity whereas E6 functions to counteract the repressive effects of p53. Both high- and low-risk HPV E7 proteins were found to bind to HIF-1α through a domain located in the N-terminus. Importantly, the ability of E7 to enhance HIF-1 activity mapped to the C-terminus and correlated with the displacement of the histone deacetylases HDAC1, HDAC4, and HDAC7 from HIF-1α by E7. Our findings describe a novel role of the E7 oncoprotein in activating the function of a key transcription factor mediating hypoxic responses by blocking the binding of HDACs.
authors.affiliation: Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Bodily
authors.forename: Kavi P M
authors.initials: KP
authors.lastname: Mehta
authors.forename: Laimonis A
authors.initials: LA
authors.lastname: Laimins
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D007527:Isoenzymes; D015603:Keratinocytes; D051379:Mice; D041681:NIH 3T3 Cells; D050725:Papillomavirus E7 Proteins / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D056572:Histone Deacetylase Inhibitors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D006655:Histone Deacetylases