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 Cancer cells make blood vessels drug resistant during chemotherapy
02.07.2020 | Hokkaido University

nachricht Novel potassium channel activator which acts as a potential anticonvulsant discovered
02.07.2020 | The Mount Sinai Hospital / Mount Sinai School of Medicine

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: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

Im Focus: ILA Goes Digital – Automation & Production Technology for Adaptable Aircraft Production

Live event – July 1, 2020 - 11:00 to 11:45 (CET)
"Automation in Aerospace Industry @ Fraunhofer IFAM"

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM l Stade is presenting its forward-looking R&D portfolio for the first time at...

Im Focus: AI monitoring of laser welding processes - X-ray vision and eavesdropping ensure quality

With an X-ray experiment at the European Synchrotron ESRF in Grenoble (France), Empa researchers were able to demonstrate how well their real-time acoustic monitoring of laser weld seams works. With almost 90 percent reliability, they detected the formation of unwanted pores that impair the quality of weld seams. Thanks to a special evaluation method based on artificial intelligence (AI), the detection process is completed in just 70 milliseconds.

Laser welding is a process suitable for joining metals and thermoplastics. It has become particularly well established in highly automated production, for...

Im Focus: A structural light switch for magnetism

A research team from the Max Planck Institute for the Structure of Dynamics (MPSD) and the University of Oxford has managed to drive a prototypical antiferromagnet into a new magnetic state using terahertz frequency light. Their groundbreaking method produced an effect orders of magnitude larger than previously achieved, and on ultrafast time scales. The team’s work has just been published in Nature Physics.

Magnetic materials have been a mainstay in computing technology due to their ability to permanently store information in their magnetic state. Current...

Im Focus: Virtually Captured

Biomechanical analyses and computer simulations reveal the Venus flytrap snapping mechanisms

The Venus flytrap (Dionaea muscipula) takes only 100 milliseconds to trap its prey. Once their leaves, which have been transformed into snap traps, have...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

 
Latest News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

A new view of microscopic interactions

02.07.2020 | Life Sciences

B-cell protectors

02.07.2020 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>