Scientists from the Max Planck Institute of Biochemistry and the University of Copenhagen have now been able to prove that the reversible attachment of acetyl groups influences virtually all functions of human cells and therefore has a much greater importance than previously assumed.
Whether it is cell division, signal transduction or ageing - all these processes are affected by acetyl groups acting as molecular switches. Therefore, these switches may prove to be a crucial factor in the development of new therapies against diseases like cancer, Alzheimer's or Parkinson's.
Proteins can be regulated by small modifications that act as molecular switches and turn certain functions on and off. One of these reversible modifications is acetylation: acetyl groups are attached to proteins and can be removed again by certain enzymes, the so-called deacetylases. This process plays a key role in many cellular processes according to the scientists' report published in todays issue of the renowned journal "Science".
Using a specifically developed technology the scientists were able, for the first time, to search for acetylation sites in the whole protein inventory of the cell. All in all, they identified more than 3600 of these switching points in almost 1800 proteins - this proves that acetylation is much more important than previously supposed and that it has broad regulatory functions. "Our results have expanded the number of known acetylation switches by a factor of six, and give us for the first time a comprehensive insight into this type of modification", says professor Matthias Mann, director of the research department "Proteomics and Signal Transduction" at the MPI of Biochemistry.
Previously scientists believed that acetylation was mainly involved in regulation of gene expression. The new study shows that practically all cellular processes are influenced, e.g. cell division, DNA-repair or signal transduction - without acetylation cells could not survive. The significance of this process is highlighted by the example of Cdc28: This protein is necessary for the budding yeast. If the acetyl-switch of Cdc28 is defect, the yeast cell dies.
Defective protein regulation plays a role in the development of numerous diseases, therefore acetylation switches are promising target points for the development of new therapies. Especially in the treatment of cancer there are already successful medications based on the inhibition of deacetylases. Two of these drugs are presently in use against certain types of leukemia.
"Another process that is influenced substantially by acetylation is ageing", explains Chunaram Choudhary, the first author of the study, who is now associate professor at the Novo Nordisk Center for Protein Research at the University of Copenhagen. Therefore manipulation of these molecular switches might also be a valuable tool for the treatment of age-related neurological diseases like Alzheimer's or Parkinson's.
Up to now, knowledge about acetylation in living cells was poor, despite its great biological and clinical significance. Due to their new technology, the scientists are now for the first time able to analyse comprehensively how acetyl-switches respond to drugs - especially with regard to the development of new medications this promises substantial progress.Original Publication:
Dr. Monika Gödde | idw
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences