title: E7 proteins from high- and low-risk human papillomaviruses bind to TGF-beta-regulated Smad proteins and inhibit their transcriptional activity.
abstract: Human papillomaviruses (HPV) infect keratinocytes of skin and mucosa. Persistent infection can lead to the formation of benign tumors. In cases of high-risk HPV, such as HPV16 or 18, these may further progress to cancer. In order to support viral replication in suprabasal keratinocytes, the HPV E7 protein employs various strategies to keep keratinocytes in cycle and counteracts anti-proliferative signals from outside. HPV16 E7 can directly interfere with transforming growth factor-beta (TGF-beta) signalling by binding to Smad proteins mediating growth arrest. It has been speculated that this property of HPV16 E7 contributes to HPV-associated carcinogenesis. Here, we show that E7 proteins from different low- and high-risk HPV types bind to Smad 1 to 4. The E7 protein from HPV1, a low-risk HPV causing plantar warts, efficiently inhibited Smad 3-induced transcription. Our data strongly indicate that the Smad-binding capacity of E7 proteins from different HPVs may preserve keratinocyte proliferation required for the productive viral life cycle rather than promoting carcinogenesis.
authors.affiliation: Institute of Virology, University of Cologne, Cologne, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Habig
authors.forename: H
authors.initials: H
authors.lastname: Smola
authors.forename: V S
authors.initials: VS
authors.lastname: Dole
authors.forename: R
authors.initials: R
authors.lastname: Derynck
authors.forename: H
authors.initials: H
authors.lastname: Pfister
authors.forename: S
authors.initials: S
authors.lastname: Smola-Hess
mesh_terms: D049109:Cell Proliferation; D015603:Keratinocytes / Q000166:cytology / Q000821:virology; D027383:Papillomaviridae / Q000737:chemistry; D050725:Papillomavirus E7 Proteins / Q000235:genetics* / Q000378:metabolism*; D051785:Smad Proteins / Q000378:metabolism*; D015533:Transcriptional Activation; D014860:Warts / Q000821:virology
chemical_list: D050725:Papillomavirus E7 Proteins; D051785:Smad Proteins