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.”
Michael van den Heuvel | alfa
Individual Receptors Caught at Work
19.10.2017 | Julius-Maximilians-Universität Würzburg
Rapid environmental change makes species more vulnerable to extinction
19.10.2017 | Universität Zürich
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
19.10.2017 | Materials Sciences
19.10.2017 | Materials Sciences
19.10.2017 | Physics and Astronomy