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 way to target advanced breast cancers
24.09.2018 | Jackson Laboratory

nachricht Neutrons produce first direct 3D maps of water during cell membrane fusion
21.09.2018 | DOE/Oak Ridge National Laboratory

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: Scientists present new observations to understand the phase transition in quantum chromodynamics

The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.

This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.

Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...

Im Focus: Patented nanostructure for solar cells: Rough optics, smooth surface

Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.

"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...

Im Focus: New soft coral species discovered in Panama

A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.

Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...

Im Focus: New devices based on rust could reduce excess heat in computers

Physicists explore long-distance information transmission in antiferromagnetic iron oxide

Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.

Im Focus: Finding Nemo's genes

An international team of researchers has mapped Nemo's genome

An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

"Boston calling": TU Berlin and the Weizenbaum Institute organize a conference in USA

21.09.2018 | Event News

One of the world’s most prominent strategic forums for global health held in Berlin in October 2018

03.09.2018 | Event News

4th Intelligent Materials - European Symposium on Intelligent Materials

27.08.2018 | Event News

 
Latest News

Matter falling into a black hole at 30 percent of the speed of light

24.09.2018 | Physics and Astronomy

NASA balloon mission captures electric blue clouds

24.09.2018 | Earth Sciences

New way to target advanced breast cancers

24.09.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>