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Penn researchers discover how key protein stops inflammation

PHILADELPHIA Researchers at the University of Pennsylvania School of Medicine recently identified how a regulatory protein called Bcl-3 helps to control the bodys inflammation response to infection by interfering a critical biochemical process called ubiquitination. While previous studies suggested Bcl-3 plays a role in immunity, this is the first report that Bcl-3 regulates inflammation by blocking ubiquitination.

Their findings, published in Science, open new avenues of exploration for developing therapies to treat infectious or inflammatory diseases, such as sepsis, diabetes, and rheumatoid arthritis.

The novelty of our study is the discovery that Bcl-3 acting on gene expression has a profound effect on inflammation, says Ruaidhri Carmody, PhD, Senior Research Investigator in the Department of Pathology and Laboratory Medicine and first author of the Science paper. By mimicking Bcl-3 activity, we may be able to create an artificial way to block the inflammatory response.

In the laboratory of senior author Youhai Chen, PhD, Associate Professor of Pathology and Laboratory Medicine, Carmody and others searched for clues as to how Bcl-3 controls inflammation by examining how Bcl-3-deficient mouse cells respond to infection. Their studies revealed that Bcl-3 interacts with p50, a protein that inhibits gene transcription by binding to DNA.

p50 turns off the DNA region coding for inflammation, halting the response to infection, explains Chen. Without Bcl-3, Chen says p50 cannot stop the inflammation response, but instead will become degraded very fast, through ubiquintination.

Ubiquitination is an intracellular system of checks and balances, where cellular proteins are flagged for disposal. During exposure to infection, Bcl-3 appears to overrule the p50 ubiquitination, stabilizing the presence of p50 on DNA and halting inflammation.

Our study identifies another layer of information that controls the infla
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
7-Aug-2007


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