Study describes how cells return to normal after responding to stress

(Embargoed) CHAPEL HILL -- New research from the University of North Carolina at Chapel Hill School of Medicine describes how cells recover from heat, cold and other stressful conditions.

The findings also could have implications for the development of new therapies for cardiovascular diseases and neurodegenerative diseases such as Alzheimer's.

The study, which appears in the March 23 issue of Nature, was led by Dr. Cam Patterson, Ernest and Hazel Craige distinguished professor of cardiovascular medicine, chief of the Division of Cardiology and director of the Carolina Cardiovascular Biology Center. Patterson also is a member of the UNC Lineberger Comprehensive Cancer Center.

The research explores the role played by the protein CHIP in the cell's response to stress. The Patterson laboratory cloned the protein in 1999.

In the setting of stress, molecules known as heat shock proteins are synthesized by the cell to provide protection against protein damage. These heat shock proteins, Hsp's, are an important part of a large protein family known as molecular chaperones. Molecular chaperones help new or distorted proteins fold into the correct shape, which is essential to their function.

"Molecular chaperones determine whether proteins are appropriately folded," Patterson said. "They help proteins to fold normally when proteins are being made, and they help the cell to find damaged proteins under stressful circumstances. Once those damaged proteins are found, the cell either tries to refold them or to get rid of them somehow."

CHIP is a co-chaperone, meaning that it associates with the molecular chaperone Hsp70 and regulates its activity. But CHIP also has another function as an ubiquitin ligase.

"Ubiquitin ligases are generally involved in tagging proteins with a signal that allows them to be recognized by the proteasome, which is the major garbage can for proteins in a cell," Patterson said. "Our model is that CHIP is the p

Contact: L.H. Lang
University of North Carolina School of Medicine

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