Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Clamping down on a cancer-causing protein

28.01.2002


Many of today’s medicines were discovered by trial and error: a substance is found which helps alleviate the symptoms of a disease, and it may take years before scientists really understand how it works. Typically they find that a drug has its effects by attaching itself to a particular molecule in a cell and blocking part of its activity, the way you might prevent someone from turning a light on or off by putting a lock over the switch. Scientists now hope to take the opposite approach, and custom-design drugs to block specific switches. To do so, they will need precise “technical diagrams” of the molecules they want to lock up. Now the Italian researcher Giulio Superti-Furga and his colleagues at the European Molecular Biology Laboratory (EMBL) have produced such a diagram of a cancer-causing molecule, and their work gives researchers a good idea of how to go about designing drugs. Their report appears in the current issue of the journal Cell.



The molecule, a protein called Abl, is produced in all human cells. Some people acquire a defect in the genetic blueprint for this molecule, causing their bodies to create a malformed version called BCR-Abl. For years researchers have known that this defective molecule is linked to forms of the deadly disease leukemia.

Abl has important jobs to perform within cells. One of its chief roles is to get information from proteins and pass it on to other molecules – like a radio operator who receives a message telling him to turn on an alarm. If Abl is defective, it might not hear incoming messages, or it might continually send off alarms, even when it hasn’t been told to do so.


One of the messages that Abl transmits tells the cell, “It’s time to divide.” Normally this signal shouldn’t be sent too often, but BCR-Abl and other defective forms of the protein are stuck in transmission mode, leading to a very high rate of cell division and thus cancer.

“Abl needs to be switched off, and one of the chief questions that people have had is whether other molecules are needed to throw the switch, or whether Abl can turn itself off,” says Giulio Superti-Furga. “We’ve now discovered that there is an internal switch that allows it to shut itself down. BCR-Abl is missing an important structural piece of the protein, a sort of clamp that holds things in the right places, and the molecule can’t stop sending signals.”

The key thing that Superti-Furga and colleagues Helma Pluk and Karel Dorey have discovered is that the clamp lies in a part of the molecule quite distant from the machinery that actually transmits signals. Clinical trials are currently being performed with a drug called STI571, which appears to directly block the transmission machinery, but some patients are able to develop resistance to the drug. This might be because the real switch is still turned on.

The EMBL researchers discovered the clamp by creating artificial versions of Abl missing certain parts, and then examining the molecule’s transmitting capabilities in the test tube. When they removed a cap section that connects itself to two major substructures of the molecule, they discovered that Abl could no longer be shut down.

“BCR-Abl doesn’t have this cap, so other parts of the the molecule probably move out of their proper positions,” Superti-Furga says. “If you imitate this by removing the cap from the normal form of Abl, or preventing the cap from clamping onto the proper parts of the molecule, the switch gets frozen.”

This explains why several roads might lead to the same result – cancer. Even if the cap structure is present, other molecules might interfere with it and break the internal switch. By showing that the cap is essential in Abl’s switch, the researchers have provided a very good place to start in designing new drugs for this specific type of cancer.



Russell Hodge | alphagalileo
Further information:
http://www.embl-heidelberg.de

More articles from Health and Medicine:

nachricht New High-Performance Center Translational Medical Engineering
26.04.2017 | Fraunhofer ITEM

nachricht A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Scientist invents way to trigger artificial photosynthesis to clean air

26.04.2017 | Materials Sciences

Ammonium nitrogen input increases the synthesis of anticarcinogenic compounds in broccoli

26.04.2017 | Agricultural and Forestry Science

SwRI-led team discovers lull in Mars' giant impact history

26.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>