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
Colorectal cancer: Increased life expectancy thanks to individualised therapies
20.02.2020 | Christian-Albrechts-Universität zu Kiel
Sweet beaks: What Galapagos finches and marine bacteria have in common
20.02.2020 | Max-Planck-Institut für Marine Mikrobiologie
The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.
Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...
Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.
Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...
Investigation of the temperature dependence of the skyrmion Hall effect reveals further insights into possible new data storage devices
The joint research project of Johannes Gutenberg University Mainz (JGU) and the Massachusetts Institute of Technology (MIT) that had previously demonstrated...
Researchers at Chalmers University of Technology, Sweden, recently completed a 5-year research project looking at how to make fibre optic communications systems more energy efficient. Among their proposals are smart, error-correcting data chip circuits, which they refined to be 10 times less energy consumptive. The project has yielded several scientific articles, in publications including Nature Communications.
Streaming films and music, scrolling through social media, and using cloud-based storage services are everyday activities now.
After helping develop a new approach for organic synthesis -- carbon-hydrogen functionalization -- scientists at Emory University are now showing how this approach may apply to drug discovery. Nature Catalysis published their most recent work -- a streamlined process for making a three-dimensional scaffold of keen interest to the pharmaceutical industry.
"Our tools open up whole new chemical space for potential drug targets," says Huw Davies, Emory professor of organic chemistry and senior author of the paper.
12.02.2020 | Event News
16.01.2020 | Event News
15.01.2020 | Event News
20.02.2020 | Physics and Astronomy
20.02.2020 | Physics and Astronomy
20.02.2020 | Power and Electrical Engineering