Researchers at IMBA – Institute of Molecular Biotechnology of the Austrian Academy of Sciences have discovered that an enzyme called HACE1 is the key regulator of the death receptor TNFR1. The TNF receptor 1 is located on the cell membrane and decides whether a cell will live or die.
In the human body there is a constant balance between cell growth and cell death. Cells that are old or diseased must be eliminated. The destruction of diseased cells plays a major role especially in infectious diseases, chronic inflammatory diseases, and cancer.
Signals coming from death receptors located on the cell surface tell the cells whether they can continue to live and divide, or if they must take the path of destruction. The orderly path is apoptosis, in which the cell dismantles itself into its individual components and is taken up by phagocytes.
But there is another path to cell destruction. It is regulated by distinct signals, and is called necroptosis. It starts via the same signals as apoptosis, but then the cells commence self-digestion. As in pathological necrosis, the cell components make their way into the extracellular space, causing an inflammatory reaction in the surrounding tissue.
The TNF (tumour necrosis factor) receptor 1 is one of the most important death receptors. Luigi Tortola and Roberto Nitsch, co-first authors of a current publication in Cell Reports, discovered that “the enzyme HACE1 is the key regulator of the TNF receptor 1. If HACE1 binds to the receptor, either the “life signal” or the signal of controlled destruction, apoptosis, is transmitted. But if HACE1 is missing, there is no more survival or apoptosis; the only option left for the cell is necroptosis.”
The consequences can be seen in the current study, in which mice that lack the HACE1 enzyme are significantly more vulnerable to intestinal inflammation, and develop bowel cancer far more often due to constant inflammation. Josef Penninger, scientific director at IMBA and last author of the publication, was surprised at the findings:
“Many years ago I was in Canada when the tumour-suppressing effect of HACE1 was discovered. No one knew then how this mechanism worked. Now we have found that this effect comes about when HACE1 intervenes directly in cell fate and determines whether the cell with live or die, and especially how it will die. That is an utterly new discovery.”
The study also showed that the intestinal inflammation proven in mice and the frequent occurrence of bowel cancer can be improved significantly through genetic blockade of the death receptor. The scientists want to use this finding for further research.
Tortola, L., Nitsch, R. et. al. (2016). The tumor suppressor Hace1 is a critical regulator of TNFR1-mediated cell fate. Cell Reports.
IMBA - Institute of Molecular Biotechnology is one of the leading biomedical research institutes in Europe focusing on cutting-edge functional genomics and stem cell technologies. IMBA is located at the Vienna Biocenter, the vibrant cluster of universities, research institutes and biotech companies in Austria. IMBA is a subsidiary of the Austrian Academy of Sciences, the leading national sponsor of non-university academic research.
Dr. Bohrgasse 3, 1030 Vienna, Austria
Tel.: +43 664 80847 – 3626
Mag. Evelyn Devuyst | idw - Informationsdienst Wissenschaft
Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care
Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
17.11.2017 | Physics and Astronomy
17.11.2017 | Health and Medicine
17.11.2017 | Studies and Analyses