Oncogenes carry the genetic blueprint for proteins that cause unregulated cell proliferation. However, these proteins usually need to interact with other partners in order to trigger the tumor growth. If this interaction is disturbed, the tumor stops growing.
Concerning the reasons for this, there has been a theory around for many years, supported by some test-tube findings. Scientists at the universities of Würzburg and Stanford now have succeeded for the first time in confirming this theory with examinations performed on a living organism. Their results are published in the current issue of the scientific journal Genes & Development.
The role of the oncogenes
Nearly all human cells have a certain group of genes, which play an important role in the formation of cancer – the so-called Myc genes. Usually these genes are not read out very frequently; they serve as a blueprint for Myc proteins, which fulfill some functions in cell growth and are required only in small amounts.
If the Myc genes do not work properly, the cells start to divide in an uncontrolled way, resulting in tumor formation. The above-mentioned team of scientists have taken a closer look at this process. "The theory that Myc proteins bind to another protein, the Miz1 protein, to regulate a group of genes important for tumor growth has already been in place since 1997," explains Martin Eilers.
Eilers is head of the Department for Physiological Chemistry II at the Biocenter of the University of Würzburg. As early as in 1988, when he conducted his postdoctoral research in San Francisco, he started to study the Myc genes and proteins. He was a member of the research team that developed the theory of the protein interaction in 1997.
Now two of the postgraduate students in his team, Judith Müller and Tobias Otto, together with their colleagues from Stanford University (California), have succeeded in confirming this theory with examinations performed on a living organism.
A genetic mutation reduces the number of cancer diseases
"Tumor cells cannot do without the continuous support from the genes responsible for their formation," says Eilers. If this support is lacking, the tumor cell collapses. "Until now the reasons for this have never been fully understood," he adds. The phenomenon can be explained by the Myc-Miz interaction.
"Tumor cells carry an intracellular program, the actual function of which is to prevent them from proliferating without control," explains Martin Eilers. In other words: A tumor cell tends to commit suicide or to refuse to work. Firstly, it can start the process of programmed cell death – a damaged cell kills itself off to protect the whole organism from greater harm. Scientists refer to this process as apoptosis. Secondly, the cell can stop its life cycle; in this case, it does no longer divide but still remains physiologically active. The technical term for this is cellular senescence.
The senescence is only prevented via the interaction with the Miz1 protein. The scientists were able to prove this by modifying the Myc gene at a specific location. As a consequence, the corresponding protein was altered in such a way that it could no longer bind effectively to Miz1. In laboratory animals carrying the mutated gene, the cancer rates were significantly reduced. The result is a bit strange: A mutated gene reduces the number of tumors. Isn't it the gene mutations that are usually responsible for a multitude of cancer diseases?
Protein interaction required
So why isn't this true in this case? "Myc needs to bind to Miz1 in order to prevent the cell from producing certain tumor-inhibiting factors," explains Martin Eilers. Myc and Miz cannot impose continuous growth on the cell unless they work together. Only their interaction can prevent the cell from implementing its normal biological aging program.
So far, the findings of the Würzburg and Stanford scientists have no direct consequences for cancer therapy. At present, the Myc-Miz complex does not represent a promising starting point – the process is too complicated for this. "We still do not know enough about its physiological function," says Eilers. Therefore, as a next step, Eilers and his team would like to clarify the role of the protein interaction in the normal development of the cell.
The interaction between Myc and Miz1 is required to antagonize TGFb-dependent autocrine signaling during lymphoma formation and maintenance. Jan van Riggelen, Judith Müller, Tobias Otto, Vincent Beuger, Alper Yetil, Peter S. Choi, Christian Kosan, Tarik Möröy, Dean W. Felsher and Martin Eilers. Genes & Development
Contact: Prof. Dr. Martin Eilers, T (0931) 31-84442, email@example.com
Gunnar Bartsch | idw
Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University
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...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction