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Scientists unlock molecular mechanism that controls cell growth

EVANSTON, Ill. Scientists at Northwestern University have identified a molecular switch that controls when and how cells grow. A team led by Richard I. Morimoto, John Evans Professor of Biology, has shown that the cell shuts down when stressed and doesnt divide until the environment is right again. These findings were published in the March 2001 issue of the journal Nature Cell Biology.

In order for living organisms to thrive, cells need to know when to grow. Environmental and physiological stress, such as that produced by toxins, a virus infection or poor nutrition, create an unhealthy environment at the molecular level. Cell growth under such conditions can result in serious problems, such as mistakes in chromosome replication or the beginnings of cancer.

"How does a cell know when its environment is bad?" said Morimoto. "Its been known for centuries that stress has a negative effect on the development and growth of organisms, but until now, we didnt know the mechanism that ties stress together with when and how cells grow."

It turns out that the signal transduction pathway, or the cascade of signals that leads to gene transcription and cell growth, is negatively regulated by a heat-shock protein called Hsp70, which acts as a stress sensor.

The protein an ancient protein found in nearly every organism on Earth patrols the cells immediate environment, in its role as constant protector. When biochemical stress builds to an unhealthy level, Hsp70 expression is rapidly activated and accumulates to high levels. The researchers showed that Hsp70 halts cell growth by binding to the protein Bag1.

In a healthy environment, Hsp70 keeps out of the way, allowing Bag1 to bind to a different protein, Raf-1, which sets the cell growth signalling process in motion. But when Bag1 is bound to Hsp70 during stressful times, it cannot bind to Raf-1 as well. When the stress ends and the numbers of Hsp70 return to normal, cell growth can continue.

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Contact: Megan Fellman
fellman@northwestern.edu
847-491-3115
Northwestern University
8-Apr-2001


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