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
Nerves control the body’s bacterial community
26.09.2017 | Christian-Albrechts-Universität zu Kiel
Ageless ears? Elderly barn owls do not become hard of hearing
26.09.2017 | Carl von Ossietzky-Universität Oldenburg
Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.
Graphene is up to the job
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
26.09.2017 | Life Sciences
26.09.2017 | Physics and Astronomy
26.09.2017 | Information Technology