The finding may one day lead to the development of targeted cancer therapies. The chains, which are added to proteins by enzymes called ubiquitin ligases, tag target proteins for destruction.

“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. [Pierce et al., Nature, (2009), doi:10.1038/nsmb.1719 Article]

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.

The research 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.

The scientists devised methods to take snapshots of ubiquitin ligase reactions at a rate of up to 100 ‘pictures’ every second,” says Deshaies. “This enables us to see things that would normally evade detection. ”

 “Using our approach,” Deshaies says, “we could see that our ubiquitin ligase builds ubiquitin chains one ubiquitin at a time.”

“Once we knew what the steps were, we calculated the rates at which they occur,” adds Pierce. “And from those rates, we were able to really describe the biology of how this system works.”

The quest doesn’t stop there, of course. “One thing we have to understand now is, how do ubiquitin ligases achieve the speeds that they do?” asks Deshaies. “What special mechanisms do they have to enable them to build chains rapidly? And the flip side of the coin: What sets the speed limit? Why can’t our ubiquitin ligase work even faster?”

Gaining insights into the ubiquitin system is important, Deshaies says, because ubiquitin ligases play a critical role in a number of human diseases, including cancer, due to their role in the regulation of the cell cycle.