Cytoplasmic Suppression of Inflammatory Signaling

This study's purpose is to assess the conformation (shape) of the anti-inflammatory protein ABIN-1 (also referred to as TNIP1). The scope of the project addresses inflammatory bowel disease (IBD). ABIN-1, independently and together with one of its binding partners, A20, has been linked to this chronic pathology. Cells deficient in ABIN-1 mount an excessive inflammatory response because they are hypersensitive to factors like those shed from bacteria. Our critical evaluation of the ABIN-1 literature, Preliminary Data in the submitted proposal, and new results for the report period confirm our hypothesis of unique conformational flexibility of ABIN-1 likely to affects its function. This idea of flexibility is significant because it helps resolve i) how ABIN-1 selects from among its many partners, ii) its quick degradation in cytokine-stimulated cells compromising its anti-inflammatory function, and iii) what protein characteristics about it could be co-opted for future cell based studies of its anti-inflammatory capacity.