Role of ATF4 in regulation of kidney gene expressions, signaling pathways and functions [mouse]

Activating transcription factor 4 (ATF4) is a transcription factor that mediates the response to stress at the cellular, tissue, and organism level. We deleted the gene encoding ATF4 in the kidney proximal tubules of the wild type (WT) and TRACK (TRAnsgenic model of Cancer of the Kidney (TRACK)) mice by using a temporal and cell type-specific approach. We show that ATF4 plays a major role in regulating the transcriptome and proteome, which, in turn, influences the metabolome and kidney functions. ATF4 deletion changed transcripts of some transporters responsible for nutrient uptake and waste excretion. It modulates metabolisms of fatty acid and glucose in the mouse model of ccRCC. It also changes metabolism in RCC4 cells. These data indicate that ATF4 plays an important role in regulation of kidney functions.