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Team finds link between stomach-cancer bug and cancer-promoting factor
Date:1/6/2010

Like other disease-causing bacteria, H. pylori have evolved to evade the body's defenses and even modify host proteins to help the bacteria survive.

Blanke and his graduate student Carlos Nossa previously had demonstrated that a protein factor released by H. pylori modifies an unidentified host protein in a manner consistent with an enzymatic reaction known as ADP-ribosylation. Other bacterial toxins, including cholera toxin and diphtheria toxin "ADP-ribosylate" host proteins in ways that enhance the survival or transmission of the bacteria that produce them.

"We were very excited about this finding, which we published in 2006," Blanke said. "We thought we had discovered a new toxin."

ADP-ribosylation can be tracked by incorporating a radio-isotope of phosphorous (32P) into a small molecule that is required for the reaction. During ADP-ribosylation, H. pylori transfers the 32P from the labeled molecule to a host protein, thereby tagging it with a radioactive fingerprint. Further analyses revealed that the radio-labeled host protein was PARP-1.

At this point, the team believed that the bacterium was ADP-ribosylating PARP-1. But when they genetically altered the functional regions of PARP-1, they completely blocked the H. pylori-dependent modification. Since PARP-1 also possesses poly-ADP-ribosylation enzymatic activity, which is necessary for its regulatory and DNA-repair function in cells, the team realized that something in the H. pylori arsenal was directly activating the PARP-1 enzymatic activity, rather than ADP-ribosylating it as they first suspected.

Additional studies validated that H. pylori indeed activates PARP-1 during infection of human gastric cells.

"These studies potentially provide a direct molecular link between H. pylori infection and the activation of a factor known to be involved in the survival of cancerous cells," Blan
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Contact: Diana Yates
diya@illinois.edu
217-333-5802
University of Illinois at Urbana-Champaign
Source:Eurekalert  

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