XIAP in Inflammatory Signalling

The understanding of NF-kappa B and MAP kinase signalling pathways is of broad scientific and medical interest, as they play major roles in a variety of inflammatory and immune reactions. Due to the ubiquitous nature of NF- kappa B, cell- and activation-specific signalling pathways leading to its activation are becoming increasingly important as targets for therapeutic interference. We have identified XIAP, originally described as an anti- apoptotic protein, as a component of the NF-kappa B, and potentially also MAP kinase signalling pathways, specifically in response to TNFalpha. Using state-of-the-art techniques including knockout cells and microarray analysis, we propose here to test the hypothesis that XIAP is a positive regulatory mechanism leading to prolonged NF-kappaB activation, and an important mediator for chronic inflammation-related diseases.

The understanding of NF-kappa B and MAP kinase signalling pathways is of broad scientific and medical interest, as they play major roles in a variety of inflammatory and immune reactions. Due to the ubiquitous nature of NF- kappa B, cell- and activation-specific signalling pathways leading to its activation are becoming increasingly important as targets for therapeutic interference. We have identified XIAP, originally described as an anti- apoptotic protein, as a component of the NF-kappa B, and potentially also MAP kinase signalling pathways, specifically in response to TNFalpha. Using state-of-the-art techniques including knockout cells and microarray analysis, we propose here to test the hypothesis that XIAP is a positive regulatory mechanism leading to prolonged NF-kappaB activation, and an important mediator for chronic inflammation-related diseases.