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Emory scientists discover unique binding method for essential cellular protein ubiquitin

Researchers at Emory University School of Medicine have uncovered new information about the molecular pathway used by ubiquitin, an essential protein that helps regulate the amounts and locations of other proteins within cells. Because ubiquitin plays a key role in cell survival, scientists have already begun to develop drugs to target parts of the ubiquitin pathway in treating diseases such as cancer.

Emory biochemist Keith Wilkinson, PhD, senior author of the study published in the March 23 issue of Cell, has been investigating ubiquitin since the late 1970s, when he was a research fellow in the laboratory of Irwin Rose, one of three scientists awarded the 2004 Nobel Prize in Chemistry for the discovery of how ubiquitin degrades proteins within cells.

In the current study, Dr. Wilkinson and first author Francisca Reyes-Turcu, graduate student, report for the first time on how ubiquitin binds to Isopeptidase T (IsoT) an enzyme responsible for disassembling chains of ubiquitin. Since the initial research on ubiquitin, scientists have understood that chains of ubiquitin direct proteins to the proteasome (a structure inside cells that breaks down protein) for degrading when they no longer are important to the functioning of the cell. "When the protein has been targeted with the ubiquitin chain to go to the proteasome, the protein gets degraded," explains Ms. Reyes-Turcu, a graduate student in Emory's Graduate Division of Biological and Biomedical Sciences.

The Emory scientists focused on IsoT because of its pivotal role in degrading, recovering and reusing ubiquitin from ubiquitin chains. "Although scientists knew that IsoT had an essential role in the recycling of ubiquitin, the structure of IsoT and how it recognized and bound to ubiquitin was not understood," said Ms. Reyes-Turcu.

Ms. Reyes-Turcu decided to focus on one area of IsoT called the "zinc finger domain," which consists of amino acid residue held together by a zinc io
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Contact: Holly Korschun
hkorsch@emory.edu
404-727-3990
Emory University Health Sciences Center
23-Mar-2006


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