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Bacterial gut biome may guide colon cancer progression
Date:4/4/2014

human innate immune system to promote healing and prevent the spread of infection.

In these studies, Rauscher and his colleagues injected anti-inflammatory proteins produced by EPEC (Enteropathogenic Escherichia coli) bacteria into colon epithelial cells. One of these proteins, NLEE, is an enzyme that targets TAB2, a human scaffolding protein involved in the transduction of chemical signals in the NF-κB pathway. Targeting TAB2 results in the inactivation of numerous inflammatory activities in the gut.

Rauscher and colleagues looked for other human proteins that could be targeted by NLEE. Remarkably, they found that NLEE also has the capability of shutting off a protein, ZRANB3 involved in DNA repair. If bacterially infected colon cells can no longer repair damage to their DNA, mutations will accumulate, which will promote cancer growth.

In addition, along with collaborators in the laboratory of Feng Shao, Ph.D., at the National Institute of Biological Sciences in Beijing, China, they demonstrated that NLEE proteins attack TAB2 and ZRANB3 by methlylating these proteinsessentially adding a single methyl moleculewhich unfolds the target proteins. NLEE appear to specifically attack a structure on TAB2 and ZRANB3 known as a "zinc finger," which is a common structural motif used in many other proteins. When the researchers determined the structure of NLEE, they found a deep cleft on the protein specific to a certain zinc finger pattern. A survey of EPEC-infected colon cells showed that this zinc finger pattern was common to at least three DNA repair enzymes, suggesting that NLEE has the capability of having widespread influence on mechanisms in the colon that typically prevent cancer growth.

"Our results suggest that some infective intestinal bacteria, which normally can simply cause gastric distress, have the capability of inducing genetic changes (by limiting repair) in our intestinal cells which could lead t
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Contact: Greg Lester
glester@wistar.org
215-898-3943
The Wistar Institute
Source:Eurekalert

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