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Why the switch stays on
Date:12/12/2007

Cellular processes, such as when to multiply, are often regulated by switches that control the frequency and timing of interactions between proteins. North Carolina State University scientists have discovered the way in which a specific protein-protein interaction prevents the cell from turning one of its switches off, leading to uncontrolled cell proliferation one of the hallmarks of cancer.

In a paper published in the December 2007 edition of the Cell Press journal Structure, the NC State researchers show for the first time that the interaction between a rogue version of a specific protein called Ras and its binding partner protein Raf can block the switch from being turned off.

The paper shows, says Dr. Carla Mattos, NC State associate professor of structural and molecular biochemistry and the lead author of the paper, that Raf secures one of the two so-called switch regions in Ras, so that the second switch can act like a closed door that isolates the key area where the overall signal switch is located. Mattos likens the abnormal protein-protein interaction to having the light permanently stuck on because the switch is inaccessible behind the closed door.

In the world of molecular biochemistry, Mattos explains, instructions for the proliferation of cells are given by cascades of protein-protein interactions controlled by on-off switches. The switch is on when the proteins can interact resulting in cell proliferation and off when they cannot. If access to the switch is blocked and the switch is stuck on, cells begin to multiply incessantly.

There are 20 existing amino acids that can be joined into chains that make up proteins. Each protein has a unique sequence of amino acids. In the chain of 189 amino acids of which Ras is composed, the position in question is at the 61st amino acid, which is normally a glutamine known to help in turning the interaction switch off. Change, or mutation, of this amino acid to an amino
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Contact: Dr. Carla Mattos
carla_mattos@ncsu.edu
919-513-2556
North Carolina State University
Source:Eurekalert

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