A NF-kappaB temporal code to ensure specificity in inflammatory signaling.

摘要

Cellular signaling pathways transmit and process signals from receptors to activate gene expression programs that regulate development, cellular life/death decisions, or the coordinated activation of the immune response. While biochemical and molecular biological studies have identified a large number of signaling proteins with diverse adaptor and/or enzymatic functions, recent work has revealed that relatively few transcriptional effector proteins are responsible for specific gene expression programs in response to a large number of stimuli. This begs the question: what mechanisms ensure stimulus-specific gene expression? It has been shown that signaling events are highly dynamic, suggesting that further progress in the understanding of cellular signaling requires quantitative studies that include the temporal dimension. My graduate work has focused on the dynamic regulation of the transcription factor Nuclear Factor kappaB (NF-kappaB) in response to specific cellular stimuli, the mechanisms that encode stimulus-specific signaling dynamics, their potential functional roles, and the utility of integrated computational and experimental studies in unraveling complex regulatory networks.