A tricky tumor virus

Jan 17, 2008

Epstein-Barr virus (EBV) is a human-pathogenic virus which belongs to the herpes virus family. Almost every adult carries EBV inside. With an infestation rate of more than 90 %, EBV is one of the most successful human viruses. Its viral genome consists of double-stranded DNA, and it is one of the few known viruses which cause cancer in humans under certain circumstances. EBV-associated cancers include lymphomas (cancer of the lymph nodes), nasopharyngeal carcinoma and gastric cancer.

A protein encoded by the virus, the latent membrane protein 1 (LMP1), is required for the uncontrolled proliferation of EBV-infected cells and, thus, the formation of cancer. Arnd Kieser and his team are studying the molecular mode of action of this EBV protein. LMP1 is a membrane-bound oncoprotein that binds certain signal molecules of its host cell and thereby critically contributes to the oncogenic transformation of the cells.

One of these signal proteins is the factor TRADD. TRADD stands for TNF-receptor 1-associated death domain protein. The scientists used TRADD knockout cell lines which they had established by removing the TRADD gene from the genome of human B-cells in order to demonstrate that TRADD is an essential factor for LMP1 function.

They found that in the absence of TRADD, LMP1 can no longer activate a cellular communication (also called: signal transduction) pathway which is crucial for cell transformation. However, TRADD's normal function within the cell includes the induction of programmed cell death which would be fatal for the virus. In fact, the scientists made the surprising observation that TRADD can no longer induce apoptosis if it is activated by the viral protein LMP1.

How does Epstein-Barr virus manage to switch off the apoptosis function of TRADD? Kieser and his colleagues discovered that the LMP1 protein possesses a unique TRADD binding domain which dictates an unusual TRADD interaction and prevents TRADD from transmitting cell death signals. Thus, LMP1 masks the apoptotic activity of TRADD. This viral TRADD-binding domain consists of the 16 carboxyterminal amino acids of the LMP1 protein and can be transplanted to cellular receptor proteins where it shows the same effects.

Hence, Epstein-Barr virus has found a unique molecular way to extinguish an undesired property of a cellular protein in order to adapt this protein to its own needs. This finding might also be the basis for a new therapeutic approach. Arnd Kieser explains: “Since the specific structure of the LMP1-TRADD interaction is most likely restricted to EBV-infected cells, it might serve as a target structure to develop specific inhibitors which interrupt the transforming signal cascade of the LMP1 oncogene.”

Source: National Research Center for Environment and Health

Explore further: Chronic inflammation linked to 'high-grade' prostate cancer

add to favorites email to friend print save as pdf

Related Stories

Adventurous bacteria

42 minutes ago

To reproduce or to conquer the world? Surprisingly, bacteria also face this problem. Theoretical biophysicists at Ludwig-Maximilians-Universitaet (LMU) in Munich have now shown how these organisms should ...

Recommended for you

Unraveling the 'black ribbon' around lung cancer

Apr 17, 2014

It's not uncommon these days to find a colored ribbon representing a disease. A pink ribbon is well known to signify breast cancer. But what color ribbon does one think of with lung cancer?

User comments : 0

More news stories

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Study says we're over the hill at 24

(Medical Xpress)—It's a hard pill to swallow, but if you're over 24 years of age you've already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.