HPV E7 viral oncoprotein disrupts transcriptional regulation of L1Md retrotransposon

Murine L1Md-A5 retrotransposon is a redox-inducible element regulated by Nrf-2/JunD and E2F/Rb-binding sites within its promoter (5′-UTR). Because the human papillomavirus (HPV) oncoprotein E7 interacts with retinoblastoma (pRb) and members of the AP1 family, studies were conducted to examine functional interactions between HPV E7, pRb, and histone deacetylase 2 (HDAC2) in the regulation of L1Md-A5. Using a transient heterologous transcription system we found that HPV E7 alone, or in combination with HDAC2, disrupted pRb-mediated L1MdA-5 transactivation. HPV E7 also ablated the transcriptional response of L1Md-A5 to genotoxic stress, but did not interfere with basal activity. We conclude that HPV E7 associates with proteins involved in the assembly of macromolecular complexes that regulate antioxidant and E2F/Rb sites within L1MdA-5 to regulate biological activity

► HPV E7 viral oncoprotein ablates L1MdA5 reactivation following genotoxic stress.
► HPV E7 disrupts retinoblastoma-mediated L1MdA5 promoter transactivation.
► The basal and carcinogen-induced activities of L1MdA5 promoter are independent of Rb repressor function.
► HPV E7 disrupts assembly of protein complexes regulating L1MdA5.