UNC team describes novel inflammatory protein function

A UNC-led team of scientists describes the function of a previously uncharacterized protein that dramatically influences inflammation.

A majority of the NLR family of proteins function as activators of . However, scientists at UNC report that a newly identified NLR protein, NLRC3, was able to inhibit a major inflammatory pathway that is controlled by a protein called NF-Kappa B. NF-Kappa B activation has been long associated with inflammation and cancer promotion. Their article appears in the August 5,2012 online publication of the journal .

The UNC team previously reported that another NLR family member, NLRP12, was also able to inhibit NF-Kappa B activation. However, in their new study, the team reported that NLRC3 inhibits this major inflammatory through a completely different mechanism. The researchers show that NLRC3 directly interacts with the molecule TRAF6 and forms a novel, previously uncharacterized protein complex described as a 'TRAFasome'. TRAF6 is a key regulator of NF-kappaB and is a critical step in the regulation of inflammation.

In pre-clinical models, the team was able to show that NLRC3 and the formation of the TRAFasome was important in regulating the during endotoxic shock, a serious hyperinflammatory process typically associated with severe infection.

Monika, Scheneider, first author of the paper and a postdoctoral research associate at UNC Lineberger Comprehensive Cancer Center, explains, "Our research reveals greater insight into the mechanisms controlling inflammation and identifies potential therapeutic targets."

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