RT Journal Article SR Electronic(1) A1 Holloway, Amy A1 Storey, AlanYR 2014 T1 A conserved C-terminal sequence of high-risk cutaneous beta-human papillomavirus E6 proteins alters localization and signalling of β1-integrin to promote cell migration JF Journal of General Virology, VO 95 IS 1 SP 123 OP 134 DO https://doi.org/10.1099/vir.0.057695-0 PB Microbiology Society, SN 1465-2099, AB Beta-human papillomaviruses (β-HPV) infect cutaneous epithelia, and accumulating evidence suggests that the virus may act as a co-factor with UV-induced DNA damage in the development and progression of non-melanoma skin cancer, although the molecular mechanisms involved are poorly understood. The E6 protein of cutaneous β-HPV types encodes functions consistent with a role in tumorigenesis, and E6 expression can result in papilloma formation in transgenic animals. The E6 proteins of high-risk α-HPV types, which are associated with the development of anogenital cancers, have a conserved 4 aa motif at their extreme C terminus that binds to specific PDZ domain-containing proteins to promote cell invasion. Likewise, the high-risk β-HPVs HPV5 and HPV8 E6 proteins also share a conserved C-terminal motif, but this is markedly different from that of α-HPV types, implying functional differences. Using binding and functional studies, we have shown that β-HPV E6 proteins target β1-integrin using this C-terminal motif. E6 expression reduced membrane localization of β1-integrin, but increased overall levels of β1-integrin protein and its downstream effector focal adhesion kinase in human keratinocytes. Altered β1-integrin localization due to E6 expression was associated with actin cytoskeleton rearrangement and increased cell migration that was abolished by point mutations in the C-terminal motif of E6. We concluded that modulation of β1-integrin signalling by E6 proteins may contribute towards the pathogenicity of these β-HPV types., UL https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.057695-0