High-risk human papillomavirus E5 oncoprotein displays channel-forming activity sensitive to small-molecule inhibitors.

Journal of Virology
Laura F WetherillAndrew Macdonald

Abstract

High-risk human papillomavirus type 16 (HPV16) is the primary causative agent of cervical cancer and therefore is responsible for significant morbidity and mortality worldwide. Cellular transformation is mediated directly by the expression of viral oncogenes, the least characterized of which, E5, subverts cellular proliferation and immune recognition processes. Despite a growing catalogue of E5-specific host interactions, little is understood regarding the molecular basis of its function. Here we describe a novel function for HPV16 E5 as an oligomeric channel-forming protein, placing it within the virus-encoded "viroporin" family. The development of a novel recombinant E5 expression system showed that E5 formed oligomeric assemblies of a defined luminal diameter and stoichiometry in membranous environments and that such channels mediated fluorescent dye release from liposomes. Hexameric E5 channel stoichiometry was suggested by native PAGE studies. In lieu of high-resolution structural information, established de novo molecular modeling and design methods permitted the development of the first specific small-molecule E5 inhibitor, capable of both abrogating channel activity in vitro and reducing E5-mediated effects on cell sign...Continue Reading

References

Feb 1, 1992·Human Pathology·M H StolerT R Broker
Apr 5, 2001·Journal of Biomedical Science·J L ChangS L Chen
Nov 9, 2002·The Journal of Biological Chemistry·Miguel Angel SanzJosé Luis Nieva
Jan 31, 2003·British Journal of Cancer·G M CliffordS Franceschi
Jun 25, 2003·Protein Expression and Purification·Dan-Hui YangFrances J Sharom
Sep 16, 2003·FEBS Letters·Maria Eugenia Gonzalez, Luis Carrasco
Mar 19, 2004·Journal of Medicinal Chemistry·Richard A FriesnerPeter S Shenkin
Sep 24, 2004·International Journal of Cancer. Journal International Du Cancer·G Hossein AshrafiM Saveria Campo
May 26, 2005·Protein Expression and Purification·F William Studier
Oct 7, 2005·Microscopy Research and Technique·Jérôme N FeigeLaurent Gelman
Mar 17, 2006·Biochemical and Biophysical Research Communications·Seong-Cheol ParkKyung-Soo Hahm
Oct 13, 2006·The Journal of Biological Chemistry·Dean ClarkeDavid Rowlands
Jun 19, 2007·Antiviral Research·Corine StGelaisStephen Griffin
Jul 10, 2007·Cancer Research·John P MaufortPaul F Lambert
Jul 16, 2008·Journal of Molecular Graphics & Modelling·Pathumwadee IntharathepSupot Hannongbua
Oct 2, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Stephen GriffinMark Harris
Jul 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Philipp LuikNicole Zitzmann
Aug 12, 2009·Proceedings of the National Academy of Sciences of the United States of America·Stephen D C Griffin
Dec 4, 2009·Journal of Virology·Ewa KrawczykRichard Schlegel
Mar 25, 2010·Cancer Research·John P MaufortPaul F Lambert
Apr 27, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Toshana L FosterStephen Griffin

❮ Previous
Next ❯

Citations

Aug 16, 2013·DNA and Cell Biology·Kristina M Giorda, Daniel N Hebert
Jun 19, 2013·Cancer Cell International·Talha Abdul HalimFarrukh Zaman
May 9, 2013·Molecular Cancer·Deborah FrenchMaria Rosaria Torrisi
Apr 20, 2014·Annual Review of Microbiology·Daniel DiMaio
Jan 26, 2016·Biochimica Et Biophysica Acta·Wolfgang B FischerDieter Heermann
Jan 6, 2016·Virology Journal·Moisés León-JuárezLeticia Cedillo-Barrón
May 30, 2015·The Journal of General Virology·Claire Scott, Stephen Griffin
Sep 24, 2013·Biochimica Et Biophysica Acta·Bo OuYang, James J Chou
Sep 17, 2013·Biochimica Et Biophysica Acta·Wolfgang B FischerChin-Pei Chen
Dec 9, 2014·Human Vaccines & Immunotherapeutics·Marcelo Nazário CordeiroAldo Venuti
Mar 17, 2015·Biochimica Et Biophysica Acta·Monoj Mon KalitaWolfgang B Fischer
Jun 5, 2013·Virology·Daniel DiMaio, Lisa M Petti
Mar 10, 2016·Annual Review of Virology·Joseph M Hyser, Mary K Estes
Dec 16, 2016·The Journal of Physical Chemistry. B·Dhani Ram Mahato, Wolfgang B Fischer
May 27, 2017·Journal of Experimental & Clinical Cancer Research : CR·Antonio Carlos de FreitasAldo Venuti
Feb 25, 2018·Expert Review of Anticancer Therapy·Marcelo Nazário CordeiroAntonio Carlos De Freitas
Jul 8, 2015·Viruses·Jose L Nieto-TorresLuis Enjuanes
Aug 11, 2015·Viruses·Vanesa Madan, Ralf Bartenschlager
Sep 15, 2017·Pathogens and Disease·Moises León-JuárezEnrique Reyes-Muñoz
Apr 10, 2018·PLoS Pathogens·Ethan L MorganAndrew Macdonald
Sep 6, 2018·International Journal of Molecular Sciences·Abida SiddiqaLawrence Banks
Aug 9, 2017·Journal of Biomolecular Structure & Dynamics·Dhani Ram Mahato, Wolfgang B Fischer
Jul 4, 2012·Nature Reviews. Microbiology·José Luis NievaLuis Carrasco
Nov 8, 2019·Journal of Medical Virology·Diogo Lisbôa BastoMiguel Ângelo Martins Moreira
Sep 3, 2019·Frontiers in Cell and Developmental Biology·Jesse M YoungMichelle A Ozbun
Aug 25, 2020·Chemistry of Heterocyclic Compounds·Vadim A Shiryaev, Yuri N Klimochkin
Dec 14, 2018·Frontiers in Microbiology·Xuelian WangYouzhong Zhang
Jul 21, 2017·Virulence·Gaurav ShrivastavaLeticia Cedillo-Barrón
May 28, 2019·Frontiers in Oncology·Tarik Gheit
Dec 26, 2015·Viruses·José Luis Nieva, Luis Carrasco
Jan 12, 2021·The Journal of General Virology·James A ScarthAndrew Macdonald
Oct 28, 2020·Molecular Cancer Research : MCR·Lourdes Gutierrez-XicotencatlFernando Esquivel-Guadarrama

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.