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
Atomic-level motion may drive bacteria's ability to evade immune system defenses
24.04.2017 | Indiana University
Two-dimensional melting of hard spheres experimentally unravelled after 60 years
24.04.2017 | University of Oxford
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
24.04.2017 | Physics and Astronomy
24.04.2017 | Materials Sciences
24.04.2017 | Life Sciences