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Evidence for direct interaction between the oncogenic proteins E6 and E7 of high-risk human papillomavirus (HPV)
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10372912/ https://www.ncbi.nlm.nih.gov/pubmed/37354975 http://dx.doi.org/10.1016/j.jbc.2023.104954 |
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author | Lim, JiaWen Lilie, Hauke Kalbacher, Hubert Roos, Nora Frecot, Desiree Isabella Feige, Maximilian Conrady, Marcel Votteler, Tobias Cousido-Siah, Alexandra Bartoli, Giada Corradini Iftner, Thomas Trave, Gilles Simon, Claudia |
author_facet | Lim, JiaWen Lilie, Hauke Kalbacher, Hubert Roos, Nora Frecot, Desiree Isabella Feige, Maximilian Conrady, Marcel Votteler, Tobias Cousido-Siah, Alexandra Bartoli, Giada Corradini Iftner, Thomas Trave, Gilles Simon, Claudia |
author_sort | Lim, JiaWen |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10372912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-103729122023-07-28 Evidence for direct interaction between the oncogenic proteins E6 and E7 of high-risk human papillomavirus (HPV) Lim, JiaWen Lilie, Hauke Kalbacher, Hubert Roos, Nora Frecot, Desiree Isabella Feige, Maximilian Conrady, Marcel Votteler, Tobias Cousido-Siah, Alexandra Bartoli, Giada Corradini Iftner, Thomas Trave, Gilles Simon, Claudia J Biol Chem Research Article 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. American Society for Biochemistry and Molecular Biology 2023-06-23 /pmc/articles/PMC10372912/ /pubmed/37354975 http://dx.doi.org/10.1016/j.jbc.2023.104954 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Lim, JiaWen Lilie, Hauke Kalbacher, Hubert Roos, Nora Frecot, Desiree Isabella Feige, Maximilian Conrady, Marcel Votteler, Tobias Cousido-Siah, Alexandra Bartoli, Giada Corradini Iftner, Thomas Trave, Gilles Simon, Claudia Evidence for direct interaction between the oncogenic proteins E6 and E7 of high-risk human papillomavirus (HPV) |
title | Evidence for direct interaction between the oncogenic proteins E6 and E7 of high-risk human papillomavirus (HPV) |
title_full | Evidence for direct interaction between the oncogenic proteins E6 and E7 of high-risk human papillomavirus (HPV) |
title_fullStr | Evidence for direct interaction between the oncogenic proteins E6 and E7 of high-risk human papillomavirus (HPV) |
title_full_unstemmed | Evidence for direct interaction between the oncogenic proteins E6 and E7 of high-risk human papillomavirus (HPV) |
title_short | Evidence for direct interaction between the oncogenic proteins E6 and E7 of high-risk human papillomavirus (HPV) |
title_sort | evidence for direct interaction between the oncogenic proteins e6 and e7 of high-risk human papillomavirus (hpv) |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10372912/ https://www.ncbi.nlm.nih.gov/pubmed/37354975 http://dx.doi.org/10.1016/j.jbc.2023.104954 |
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