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Penn researchers find new role for cancer protein p53
Date:3/2/2011

PHILADELPHIA - The gene for the protein p53 is the most frequently mutated in human cancer. It encodes a tumor suppressor, and traditionally researchers have assumed that it acts primarily as a regulator of how genes are made into proteins. Now, researchers at the University of Pennsylvania School of Medicine show that the protein has at least one other biochemical activity: controlling the metabolism of the sugar glucose, one of body's main sources of fuel. These new insights on a well-studied protein may be used to develop new cancer therapies.

Xiaolu Yang, PhD, associate professor of Cancer Biology at the Abramson Family Cancer Research Institute, along with Mian Wu, PhD, at the University of Science and Technology of China and Nanjing University, report in the current issue of Nature Cell Biology that p53 controls a molecular crossroads in the cell's glucose metabolic pathway.

They found that p53 physically binds to and inhibits an enzyme -- glucose-6-phosphate dehydrogenase (G6PD), which catalyzes the first step of the pathway. If p53 can't do its intended job, cells grow out of control.

Blocking this pathway shunts glucose away from energy storage and towards making genetic building blocks and lipids that contribute to cells' proliferation. p53 normally serves to dampen synthesis of molecules and cell reproduction by forcing the cell to take up less glucose.

In tumors, more than half of which carry mutations in the p53 gene, this routing function is abolished, enabling cells to build biomass and divide with abandon.

The findings provide a biochemical explanation for the Warburg effect, which explains how cancer cells, regardless of type, seem inevitably to boost their glucose consumption, but not in an energy efficient way.

"We found a connection between the most frequently mutated gene in cancer cells and how that mutation contributes to tumor growth," says Yang.

Making a Choice
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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