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Brown researchers make major signal transduction discovery
Date:10/4/2007

PROVIDENCE, R.I. [Brown University] The chemical process known as acetylation plays a central role in cytokine receptor signal transduction a fundamental biochemical cascade inside cells that controls the activity of antiviral and tumor-suppressing genes.

A team of cell biologists led by Eugene Chin, M.D., a research professor at The Warren Alpert Medical School of Brown University and a staff researcher at Rhode Island Hospital, reports its findings in the journal Cell. Their results are surprising.

Scientists have long known that phosphorylation, an amino acid modifying process in proteins, is critical for switching receptors on and off on the surface of cells. Chin and his team studied how type 1 interferon binds to a receptor complex, known as the IFN-α receptor, on the cell surface to trigger an immune response. Chin and his team found that acetylation, another chemical process that modifies amino acids, plays a central role in activating interferon receptors.

Interferons play a crucial role in the bodys defense against infection and uncontrolled cell growth. Type 1 interferon is widely used to treat hepatitis B and C and cancers such as melanoma and leukemia.

This is a major discovery in the field of signal transduction, Chin said. Tyrosine phosphorylation has so far been considered the major player in signal transduction. But what we discovered challenges this concept. We found another player acetylation in the process.

In their experiments, Chin and his team looked at how cells respond to type 1 interferon, a protein produced in response to a viral infection or other immune trigger. The researchers found that type 1 interferon receptors, which are found in every cell in the body, call up cytoplasmic CREB-binding protein, or CBP, to move up to the cell surface. CPB acetylates these receptors. That, in turn, sparks a biochemical cascade that attracts more proteins to create a complex called ISGF3. To a
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Contact: Wendy Lawton
Wendy_Lawton@brown.edu
401-863-1862
Brown University
Source:Eurekalert

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