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Caltech scientists show how ubiquitin chains are added to cell-cycle proteins
Date:12/2/2009

PASADENA, Calif.Researchers from the California Institute of Technology (Caltech) have been able to view in detail, and for the first time, the previously mysterious process by which long chains of a protein called ubiquitin are added by enzymes called ubiquitin ligases to proteins that control the cell cycle. Ubiquitin chains tag target proteins for destruction by protein-degrading complexes in the cell.

"We found that ubiquitin ligases build ubiquitin chains very rapidly by transferring ubiquitins one at a time," says Raymond Deshaies, professor of biology at Caltech and Howard Hughes Medical Institute investigator.

Their findings, and the innovative process by which they were obtained, are described in this week's issue of the journal Nature.

Ubiquitin is one of nature's most unusual proteins. Unlike most of its protein brethren, ubiquitin has to be physically attached to other proteins to do its job.

"As its name implies, ubiquitin is found in essentially every kind of eukaryotic cell," says Caltech graduate student Nathan Pierce, the Nature paper's lead author.

In their Nature paper, the Caltech team looked at the process of ubiquitylation, the method by which ubiquitin and ubiquitin chains are added to target proteins. The target proteins used in the study, cyclin E and β-Catenin, are both involved in controlling the cell cycle.

It was already known, Pierce explains, that the addition of a chain of four or more ubiquitins to a target protein marks that protein for annihilation. The destruction of cyclin E is critical for the accurate replication of DNA, while the degradation of β-Catenin keeps cells from dividing during development at the wrong time. If β-Catenin is not degraded, cells proliferate excessively and become predisposed to tumorigenesis. Meanwhile, cells that don't degrade cyclin E accumulate DNA damage and mutations, which can help fuel the unchecked
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Contact: Lori Oliwenstein
lorio@caltech.edu
626-395-3631
California Institute of Technology
Source:Eurekalert  

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