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Chemical tags likely to affect metabolism, cancer development
Date:2/18/2010

y a role in the other half of the cell, the cytoplasm.

So they separated the nucleus and the cytoplasm of primary liver cells, and then took a chemical census of the cytoplasm's contents using a technology called mass spectroscopy. They identified approximately a thousand new proteins that are acetylated, greatly expanding the previously recognized repertoire of fifty.

At first, the researchers were overwhelmed by such a large number of proteins to study, said Xiong. But then they began notice a pattern -- almost every metabolic enzyme was acetylated, presumably because their starting material was liver, an organ rich in metabolic activity.

"We think that acetylation is likely to play a very extensive role in regulation of many different cellular processes, not just metabolism," said Xiong.

Xiong and his colleagues looked at the acetylation of one enzyme from each of the four major metabolic pathways. They found that by altering the metabolic fuels that feed into these pathways they could alter the level of acetylation.

In addition, the researchers discovered that blocking acetylation chemically or genetically affected these metabolic enzymes in a number of different ways, either by stimulating its activity, inhibiting it, or degrading the protein itself. They suspect that acetylation is important for coordinating not only the players within a metabolic pathway but also between different pathways.

The next step is to take their finding in normal cells and see how it can inform their study of tumor cells. The researchers are in the process of looking at each metabolic enzyme, one-by-one, to see which one displays the most disparate acetylation patterns between normal and cancer cells. They will then try to use the very same proteins that tack on or pull off those acetyl groups called acetylases or deacetylases, respectively -- to modify acetylation and thwart cancer development.


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Contact: Les Lang
llang@med.unc.edu
919-966-9366
University of North Carolina School of Medicine
Source:Eurekalert  

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