Featured Research

from universities, journals, and other organizations

Cervical cancer: First 3-D image of an HPV oncoprotein

Date:
February 14, 2013
Source:
Le Centre national de la recherche scientifique (CNRS)
Summary:
For the first time, researchers have solved the three-dimensional structure of an important oncoprotein involved in cell proliferation and in the development of the human papilloma virus (HPV). Type 16 (HPV 16), which causes cervical cancer, is the most dangerous of human papilloma viruses. This work, published in Science on 8 February 2013, should make it possible to identify and improve medication to block the protein and prevent it from causing tumors.

For the first time, researchers from the Laboratoire biotechnologie et signalisation cellulaire at the Strasbourg-based Ecole supérieure de biotechnologie (CNRS/Université de Strasbourg) and Institut de génétique et de biologie moléculaire et cellulaire (CNRS/Université de Strasbourg/Inserm) have solved the three-dimensional structure of an important oncoprotein involved in cell proliferation and in the development of the human papilloma virus (HPV). Type 16 (HPV 16), which causes cervical cancer, is the most dangerous of human papilloma viruses. This work, published in Science on 8 February 2013, should make it possible to identify and improve medication to block the protein and prevent it from causing tumors.

Cervical cancer is one of the most common cancers in the world, ranking second in terms of mortality among women. It is caused by so-called "high-risk" (1) human papilloma viruses (HPV), of which type 16 (HPV 16) is the most dangerous. After infecting a healthy cell, HPV must stimulate it to multiply in order to reproduce itself. The viral proteins E6 and E7 cause cell proliferation and the development of cervical cancer, which is why they are known as "oncoproteins."

For the first time, researcher Gilles Travé and his team at the laboratoire Biotechnologie et signalisation cellulaire (CNRS/University of Strasbourg) working in collaboration with researchers led by Jean Cavarelli and Bruno Keiffer of the Institut de génétique et de biologie moléculaire et cellulaire (CNRS/University of Strasbourg/Inserm) have solved the three-dimensional structures of E6 proteins in type-16 human papilloma virus and its type 1 bovine equivalent (BPV 1). The same researchers had already solved the structure of E6 in HPV 16 in 2012 (2), but this time the E6 proteins have been "caught" in the process of capturing target cellular proteins. The complete structure of an E6 protein-which is very tricky to produce in the laboratory-had remained unsolved for almost 30 years.

Success depended on two factors: the development of methods for isolating protein E6 as well as the use of nuclear magnetic resonance (NMR) (3) and crystallography (4) techniques. Having dealt with various aggregation and purification problems, the researchers succeeded in obtaining protein E6. The challenge then was to keep it in its folded form (so as to preserve its ability to organize itself and thus be biologically active). NMR and crystallography data made it possible to determine the structure of the E6 protein and obtain a high-resolution 3D "photograph."

The three-dimensional structure of the E6 protein capturing its target reveals the exact molecular mechanism of its carcinogenic activity. It also explains the protein's remarkable ability to act as a viral terrorist and hijack many of the functions of the infected cell. This breakthrough is crucial for cervical cancer treatment, as it should make it possible to identify and improve medication to prevent the protein from causing tumors.

Notes

(1) High-risk strains : HPV viruses are classified as high-risk or low-risk depending on their ability to cause cancer. The main high-risk strains of human papilloma virus are types 16, 18, 31, 33 and 51.

(2) Zanier K, Ould M'hamed Ould Sidi A, Rybin V, Boulade-Ladame C, Rybin V, Chapelle A, Atkinson RA, Kieffer B, Travé G. Solution structure analysis of the HPV16 E6 oncoprotein reveals a self-association mechanism required for E6-mediated degradation of p53. Structure 2012, 20(4):604-617.

(3) Nuclear magnetic resonance: a method for studying biological molecules, which measures resonance in the nuclei of certain atoms. It is used to determine the structure of proteins.

(4) Crystallography: a method for determining the atomic structure of a crystallised protein by x-ray diffraction.


Story Source:

The above story is based on materials provided by Le Centre national de la recherche scientifique (CNRS). Note: Materials may be edited for content and length.


Journal Reference:

  1. K. Zanier, S. Charbonnier, A. O. M. O. Sidi, A. G. McEwen, M. G. Ferrario, P. Poussin-Courmontagne, V. Cura, N. Brimer, K. O. Babah, T. Ansari, I. Muller, R. H. Stote, J. Cavarelli, S. Vande Pol, G. Trave. Structural Basis for Hijacking of Cellular LxxLL Motifs by Papillomavirus E6 Oncoproteins. Science, 2013; 339 (6120): 694 DOI: 10.1126/science.1229934

Cite This Page:

Le Centre national de la recherche scientifique (CNRS). "Cervical cancer: First 3-D image of an HPV oncoprotein." ScienceDaily. ScienceDaily, 14 February 2013. <www.sciencedaily.com/releases/2013/02/130214103707.htm>.
Le Centre national de la recherche scientifique (CNRS). (2013, February 14). Cervical cancer: First 3-D image of an HPV oncoprotein. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2013/02/130214103707.htm
Le Centre national de la recherche scientifique (CNRS). "Cervical cancer: First 3-D image of an HPV oncoprotein." ScienceDaily. www.sciencedaily.com/releases/2013/02/130214103707.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) — Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) — A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) — More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) — Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins