A nuclear phospholipid biosynthetic enzyme regulates cell proliferation and differentiation

CTP:phosphocholine cytidylyltransferase α (CCTα) is the major enzyme isoform that catalyzes the rate-limiting step in the CDP-choline pathway for the synthesis of phosphatidylcholine (PC), the most abundant phospholipid in mammalian cells. Unlike the initiating and terminal enzymes in CDP-choline pathway that are in the cytoplasm, CCTα is localized in the nucleus. From its nuclear locale CCTα regulates the synthesis of PC required for the proliferation and survival of ras-transformed cancer cells, and the deposition of triacylglycerides in lipid droplets during adipocyte differentiation. The regulation of PC synthesis observed in these cell models involves both increased expression and lipid-dependent activation of CCTα at the nuclear envelope. CCTα could be an important target to prevent the pathophysiological consequences of defective
cell growth and differentiation.