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Cooperative action of two proteins causes damaged cells to "self-destruct"

REHOVOT, Israel -- December 20, 1999 -- Researchers at the Weizmann Institute of Science have recently deciphered part of the cellular events underlying apoptosis - programmed cell death. Their findings, published in Nature earlier this summer, provide important insights into cancer pathologies and their potential cures.

It is known that all cells contain a built-in suicide mechanism. This process is vital to normal embryonic development and tissue maintenance. It is the body's means of ridding itself of damaged or surplus cells.

Failure of the apoptosis or suicide mechanism can be deadly. Cell mutations occur regularly in every organism due to environmental factors, such as ultraviolet radiation and chemical toxins, as well as natural cell processes. If left unchecked, the damaged cells will continue to proliferate, often leading to life-threatening diseases, such as cancer.

This "emergency" suicide pathway is designed to reverse or mitigate mutation induced damage, explains Prof. Yosef Shaul of Weizmann's Molecular Genetics Department. It is an intricate check and balance system controlled by a tightly orchestrated team of genes and their respective proteins. These genes interact with each other in an environment characteristic of computer programming, where they respond to If, Then, Else signals concerning cellular functioning. The protein products of these genes will initially attempt to repair the damaged DNA. If they are unsuccessful, they command the cell to "self-destruct." In the third, and worst case scenario, both DNA repair and apoptosis fail, and the result is usually the growth of a tumor.

Yet who are these protein "players", and most importantly, how do they interact? This is what Shaul and colleagues, Prof. Moshe Oren, and Drs. Reuven Agami and Giovanni Blandino, set out to understand.

They began with c-Abl - a major regulator of cell growth which, when mutated, can act as an oncogene - a gene that causes cancer. E
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Contact: Jeffrey J. Sussman, Assist. V.P., Communications
jeffrey@acwis.org
212-779-2500 ext.121
American Committee for the Weizmann Institute of Science
19-Dec-1999


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