A broad response to intracellular long-chain polyphosphate in human cells

Polyphosphates (polyP) are ancient molecules comprised of inorganic phosphates joined by high energy phosphoanhydride bonds in chains of 3-1000 units in length. In this study, we describe a system to produce polyP in mammalian cells by ectopic expression of the E. coli ppk1+ gene. Production of the EcPpk1 protein results in polyP accumulation throughout the cell, including the nucleus. Using transcriptomic and proteomic analyses, we demonstrate a broad impact of polyP on diverse pathways, including activation of the ERK1/2-ERG1 signaling axis. PolyP accumulation also results in redistribution of several chromatin bound proteins and a translation initiation factor from the nucleus to the cytoplasm. Our work will serve as a novel resource to interrogate polyP biology in higher eukaryotes.