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: AstraZeneca cancer drug, companion test approved

add to favorites email to friend print save as pdf

Related Stories

Strong quake hits east Indonesia; no tsunami threat

30 minutes ago

A strong earthquake struck off the coast of eastern Indonesia on Sunday evening, but there were no immediate reports of injuries or damage, and authorities said there was no threat of a tsunami.

Britain's UKIP issues online rules after gaffes

6 minutes ago

UK Independence Party (UKIP), the British anti-European Union party, has ordered a crackdown on the use of social media by supporters and members following a series of controversies.

Sony saga blends foreign intrigue, star wattage

16 minutes ago

The hackers who hit Sony Pictures Entertainment days before Thanksgiving crippled the network, stole gigabytes of data and spilled into public view unreleased films and reams of private and sometimes embarrassing ...

China's Xiaomi raises more than $1 bn in funding

35 minutes ago

China's top smartphone seller Xiaomi Corp. is raising more than $1 billion in a fresh round of funding, a move which would raise its valuation above $45 billion, a report said Sunday.

Recommended for you

Putting the brakes on cancer

Dec 19, 2014

A study led by the University of Dundee, in collaboration with researchers at our University, has uncovered an important role played by a tumour suppressor gene, helping scientists to better understand how ...

Peanut component linked to cancer spread

Dec 19, 2014

Scientists at the University of Liverpool have found that a component of peanuts could encourage the spread and survival of cancer cells in the body.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.