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Cellular pathway includes a 'clock' that steers gene activity

Researchers from The Johns Hopkins University and other institutions have discovered a biochemical "clock" that appears to play a crucial role in the way information is sent from the surface of a cell to its nucleus. These messages can cause the cell to thrive or commit suicide, and manipulating them could lead to new treatments for cancer and other diseases, the researchers say.

The findings, based on lab experiments conducted at Cal Tech and computer models developed at Johns Hopkins, are reported in the Nov. 8 issue of the journal "Science."

Scientists have known that living cells send messages from their surfaces to their nuclei by setting off a chain of chemical reactions that pass the information along like signals traveling over a telephone wire. Such reaction chains are called signaling pathways. But while studying one such reaction chain called the NF-kappaB pathway within mouse cells, the university researchers learned that the signal transmission process is even more complicated.

"We found that if the pathway was activated for a short time, a single pulse of activity was delivered to the nucleus, like a single tick of a clock, activating a set of genes," said Andre Levchenko, assistant professor in the Department of Biomedical Engineering at Johns Hopkins. "But longer activation could produce more pulses and induce a larger gene set. We believe that the timing between pulses is critical. If too much or too little time elapsed, the genetic machinery would not respond properly."

Levchenko, a lead author on the "Science" paper, and his colleagues concluded that the signaling pathway inside a cell was serving as much more than a simple wire. "It was not just carrying the information, it was processing it," he said. "The pathway was operating like a clock with a pendulum, delivering the signal at particular intervals of time in a way that could resonate with the behavior of the genes in the nucleus."

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Contact: Phil Sneiderman
prs@jhu.edu
410-516-7907
Johns Hopkins University
7-Nov-2002


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