Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

How Signal Molecules for the Formation of Various Cell Types Are Controlled

03.12.2012
Researchers study influence of chemically produced variants of natural indirubin

The regulation of important signal molecules that are critical for the formation of various cell types can be influenced by a chemically produced variant of indirubin, a natural material used in traditional Chinese medicine. This was shown by scientists from Heidelberg University, Kaiserslautern and Jena.

The researchers were also able to demonstrate for the first time that these signal molecules in the cell – regulatory SMAD proteins – are not only controlled through regulation of their activation but also through the available quantity of signal molecules in the non-activated state. Because cellular differentiation as well as tumour growth are tied to these processes, the studies suggest a new approach for both the preparation of induced pluripotent stem cells and the development of tumour treatments. The results of the research were published in the journal “Chemistry & Biology”.

Cellular differentiation decides which functions can be assumed and carried out by cells in the body. Their precise regulation has a decisive influence on embryonic development and later also plays an essential role in maintaining the activity of organs. After toxic damage, among other things, it is important that cells can react appropriately to limit damage and regenerate the tissue. This requires close communication between the cells, which is controlled by numerous signal molecules. “Only when all the parts of a signal path are present, cells can react to the signals from the environment with a coordinated programme. If one of these components is missing, the proper cellular response is inhibited”, explains Prof. Dr. Stefan Wölfl from Heidelberg University's Institute of Pharmacy and Molecular Biotechnology.

How cellular differentiation is controlled during embryonic development and in the mature organism significantly depends on the family of TGFß/BMP growth factors. Representatives of these specific signal molecules also participate in the genesis and development of tumour diseases. Through their work, the researchers have demonstrated that the cells themselves influence how sensitively they react to growth factor signals. This occurs through the availability of the complementary signal mediators within the cell adapting to the given situation. The amount of available regulatory SMAD proteins (R-Smad proteins) in the cell is controlled on the level of synthesis, but in particular through the control of their degradation. This is performed by a special control system present in every cell. This ubiquitin proteasome system makes it possible for cellular proteins to be degraded in a controlled manner.
Earlier research already demonstrated that the degradation of activated R-Smad proteins occurs through the ubiquitin proteasome system, resulting in termination of the signals. “Our results now prove that the reservoir of non-activated R-SMAD signal mediators is also strictly controlled. This prevents corresponding external signals from activating an internal programme”, says Prof. Wölfl. “For example, if growing tumour cells are dependent on this signal, these cells could be kept from surviving and cell death may even occur if the signal mediators could be deliberately removed.” According to Prof. Wölfl, R-Smad proteins are also important mediators in cellular differentiation. “Reducing or removing these signal mediators from stem cells would cause them to no longer react to differentiation signals, so they would retain their stem cell properties as a result.”

In their experiments, the researchers worked with a variant of the natural product indirubin that they chemically synthesised. The studies showed that the indirubin derivative led to a degradation of the R-Smad proteins in human cells. Thus, the signals transmitted by the TGFß/BMP growth factors are blocked. In this procedure, the indirubin variant intervenes in various processes that all contribute to depleting the concentration of R-Smad proteins in the cell. In particular, the activity of specific regulating enzymes called ubiquitin proteases is diminished, which protect proteins from degradation in the ubiquitin proteasome system.

The research was funded by the Federal Ministry of Education and Research (BMBF) within a joint research project focussed on medical system biology. The research team at the Institute of Pharmacy and Molecular Biotechnology of Heidelberg University collaborated with scientists from the University of Kaiserslautern and the Jena University Hospital as well as the Heidelberg University Hospital’s Institute of Human Genetics.

Original publication:
X. Cheng, H. Alborzinia, K.H. Merz, H. Steinbeisser, R. Mrowka, C. Scholl, I. Kitanovic, G. Eisenbrand, S. Wölfl: Indirubin Derivatives Modulate TGFβ/BMP Signaling at Different Levels and Trigger Ubiquitin-Mediated Depletion of Nonactivated R-Smads, Chemistry & Biology, Volume 19, Issue 11, 21 November 2012, Pages 1423-1436, doi: 10.1016/j.chembiol.2012.09.008

Contact:
Prof. Dr. Stefan Wölfl
Institute of Pharmacy and Molecular Biotechnology
Phone: +49 (0)6221 54-4878, wolfl@uni-hd.de

Communications and Marketing
Press Office, phone: +49 (0)6221 54-2311
press@rektorat.uni-heidelberg.de

Marietta Fuhrmann-Koch | idw
Further information:
http://www.uni-heidelberg.de

More articles from Life Sciences:

nachricht MACC1 Gene Is an Independent Prognostic Biomarker for Survival in Klatskin Tumor Patients
31.08.2015 | Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft

nachricht Fish Oil-Diet Benefits May be Mediated by Gut Microbes
28.08.2015 | University of Gothenburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Increasingly severe disturbances weaken world's temperate forests

Longer, more severe, and hotter droughts and a myriad of other threats, including diseases and more extensive and severe wildfires, are threatening to transform some of the world's temperate forests, a new study published in Science has found. Without informed management, some forests could convert to shrublands or grasslands within the coming decades.

"While we have been trying to manage for resilience of 20th century conditions, we realize now that we must prepare for transformations and attempt to ease...

Im Focus: OU astrophysicist and collaborators find supermassive black holes in quasar nearest Earth

A University of Oklahoma astrophysicist and his Chinese collaborator have found two supermassive black holes in Markarian 231, the nearest quasar to Earth, using observations from NASA's Hubble Space Telescope.

The discovery of two supermassive black holes--one larger one and a second, smaller one--are evidence of a binary black hole and suggests that supermassive...

Im Focus: What would a tsunami in the Mediterranean look like?

A team of European researchers have developed a model to simulate the impact of tsunamis generated by earthquakes and applied it to the Eastern Mediterranean. The results show how tsunami waves could hit and inundate coastal areas in southern Italy and Greece. The study is published today (27 August) in Ocean Science, an open access journal of the European Geosciences Union (EGU).

Though not as frequent as in the Pacific and Indian oceans, tsunamis also occur in the Mediterranean, mainly due to earthquakes generated when the African...

Im Focus: Self-healing landscape: landslides after earthquake

In mountainous regions earthquakes often cause strong landslides, which can be exacerbated by heavy rain. However, after an initial increase, the frequency of these mass wasting events, often enormous and dangerous, declines, in fact independently of meteorological events and aftershocks.

These new findings are presented by a German-Franco-Japanese team of geoscientists in the current issue of the journal Geology, under the lead of the GFZ...

Im Focus: FIC Proteins Send Bacteria Into Hibernation

Bacteria do not cease to amaze us with their survival strategies. A research team from the University of Basel's Biozentrum has now discovered how bacteria enter a sleep mode using a so-called FIC toxin. In the current issue of “Cell Reports”, the scientists describe the mechanism of action and also explain why their discovery provides new insights into the evolution of pathogens.

For many poisons there are antidotes which neutralize their toxic effect. Toxin-antitoxin systems in bacteria work in a similar manner: As long as a cell...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Networking conference in Heidelberg for outstanding mathematicians and computer scientists

20.08.2015 | Event News

Scientists meet in Münster for the world’s largest Chitin und Chitosan Conference

20.08.2015 | Event News

Large agribusiness management strategies

19.08.2015 | Event News

 
Latest News

Production research by Fraunhofer IAO honored with three awards at the ICPR 2015

31.08.2015 | Awards Funding

Single-Crystal Phosphors Suitable for Ultra-Bright, High-Power White Light Sources

31.08.2015 | Materials Sciences

Manchester Team Reveal New, Stable 2D Materials

31.08.2015 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>