Evidence for direct interaction between the oncogenic proteins E6 and E7 of high-risk human papillomavirus (HPV) - Archive ouverte HAL Access content directly
Journal Articles Journal of Biological Chemistry Year : 2023

Evidence for direct interaction between the oncogenic proteins E6 and E7 of high-risk human papillomavirus (HPV)

Jiawen Lim
  • Function : Author
Hauke Lilie
  • Function : Author
Hubert Kalbacher
  • Function : Author
Nora Roos
  • Function : Author
Desiree Isabella Frecot
Maximilian Feige
  • Function : Author
Marcel Conrady
Tobias Votteler
  • Function : Author
Alexandra Cousido-Siah
Giada Corradini Bartoli
  • Function : Author
Thomas Iftner
  • Function : Author
Gilles Trave
Claudia Simon

Abstract

Human papillomaviruses (HPVs) are DNA tumor viruses that infect mucosal and cutaneous epithelial cells of more than 20 vertebrates. High-risk HPV causes about 5% of human cancers worldwide, and the viral proteins E6 and E7 promote carcinogenesis by interacting with tumor suppressors and interfering with many cellular pathways. As a consequence, they immortalize cells more efficiently in concert than individually. So far, the networks of E6 and E7 with their respective cellular targets have been studied extensively but independently. However, we hypothesized that E6 and E7 might also interact directly with each other in a novel interaction affecting HPV-related carcinogenesis. Here, we report a direct interaction between E6 and E7 proteins from carcinogenic HPV types 16 and 31. We demonstrated this interaction via cellular assays using two orthogonal methods: coimmunoprecipitation and flow cytometry-based FRET assays. Analytical ultracentrifugation of the recombinant proteins revealed that the stoichiometry of the E6/E7 complex involves two E7 molecules and two E6 molecules. In addition, fluorescence polarization showed that (I) E6 binds to E7 with a similar affinity for HPV16 and HPV31 (in the same micromolar range) and (II) that the binding interface involves the unstructured N-terminal region of E7. The direct interaction of these highly conserved papillomaviral oncoproteins may provide a new perspective for studying HPV-associated carcinogenesis and the overall viral life cycle.

Dates and versions

hal-04304627 , version 1 (24-11-2023)

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Jiawen Lim, Hauke Lilie, Hubert Kalbacher, Nora Roos, Desiree Isabella Frecot, et al.. Evidence for direct interaction between the oncogenic proteins E6 and E7 of high-risk human papillomavirus (HPV). Journal of Biological Chemistry, 2023, 299 (8), pp.104954. ⟨10.1016/j.jbc.2023.104954⟩. ⟨hal-04304627⟩
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