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, firstname.lastname@example.org
Gunnar Bartsch | idw
Complementing conventional antibiotics
24.05.2018 | Goethe-Universität Frankfurt am Main
Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
24.05.2018 | Ecology, The Environment and Conservation
24.05.2018 | Medical Engineering
24.05.2018 | Physics and Astronomy