ITCH K63-ubiquitinates the NOD2 binding protein, RIP2, to influence inflammatory signaling pathways.

ABSTRACT:

Background

The inability to coordinate the signaling pathways that lead to proper cytokine responses characterizes the pathogenesis of inflammatory diseases such as Crohn's disease. The Crohn's disease susceptibility protein, NOD2, helps coordinate cytokine responses upon intracellular exposure to bacteria, and this signal coordination by NOD2 is accomplished, in part, through K63-linked polyubiquitin chains that create binding surfaces for the scaffolding of signaling complexes.

Results

In this work, we show that the NOD2 signaling partner, RIP2, is directly K63-polyubiquitinated by ITCH, an E3 ubiquitin ligase that when lost genetically causes widespread inflammatory disease at mucosal surfaces. We show that ITCH is responsible for RIP2 polyubiquitination in response to in

SUBMITTER: Tao M 

PROVIDER: S-EPMC2741418 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature