NF-kappaB: Orchestration of the Inflammatory Response

California Institute Of Technology, Pasadena CA

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Abstract

This project is a continuation of a line of investigation we started more than 20 years ago. We then discovered a protein, called NF-KB, that subsequent work has shown to playa key role in inflammation and immunity. Here we propose four lines of investigation (aims) that seek to increase our knowledge of the roles of NF-KB in the inflammatory response. Inflammation is a process that continues for days following an initiating stimulus and NF-KB plays a role throughout: our first aim is to understand the temporal control processes that allow the inflammatory response to unfold in an orderly manner. Our second aim is to probe the role played by an enigmatic regulator of NF-KB responses called B94. It potentiates induction of some genes by NF-KB but there is no mechanistic or physiological understanding of its effects. NF-KB is extensively modified as part of its mode of action: our final two aims are to investigate previously uncharacterized modifications for which we have preliminary indications of importance: methylation and glycosylation.