PIKKing a way to regulate inflammation:

Abstract

The phosphoinositide-3-kinase like kinases are a family of very large protein kinases. These PI3-kinase like kinase (PIKK) proteins have well-established roles in detection and repair of damage to the genome, regulation of the transcriptome and cellular metabolism. Recently there has emerged, evidence for links between these proteins and inflammation. While some of these links come from an increased understanding of the impacts of damage to the cell on inflammatory responses, others suggest that PIKK proteins also have direct roles in regulation of immune responses. Particularly evident is the link between DNA damage and innate immune response pathways. Here, we review recent findings on the PIKK family of proteins and how they impact on inflammation, particularly activation of the innate immune system. The phosphoinositide 3-kinase like kinase (PIKK) family of proteins play diverse roles in the maintenance of cellular homeostasis and it is becoming increasingly clear that this includes regulation of inflammation. A key emerging theme is the link between DNA damage responses and activation of 'cytosolic DNA' sensing pathways.