Intracellular amino acid sensing and mTORC1-regulated growth: New ways to block an old target?

摘要: Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) is a multicomponent, nutrient-sensitive protein that implicated in wide range major human diseases. mTORC1 responds to both growth factors and changes local amino acid levels. Until recently, the intracellular acid-sensing mechanism regulates had remained unexplored. However, studies cells culture have demonstrated response stimulation, mTOR (a conserved member PI3K superfamily) shuttled late endosomal lysosomal compartments, where it binds Ragulator-Rag assembled into active mTORC1. Members proton-assisted transporter (PAT/SLC36) family been identified as critical components system present membranes. These discoveries not only highlight several new potential drug targets could impact selectively on activity cancer cells, but also provide novel insights strategies used by such outcompete their neighbors factor- nutrient-depleted conditions. In this review, recent mechanistic how controlled acids for selective targeting regulatory input are discussed.