SREBP Activity Is Regulated by mTORC1 and Contributes to Akt-Dependent Cell Growth

TLDR

Cell growth requires coordination with metabolic processes for macromolecule synthesis, and the PI3‑kinase/Akt pathway promotes growth through activation of mTORC1. The study demonstrates that Akt‑dependent lipogenesis and cell growth require mTORC1 activity, as rapamycin blocks SREBP1 nuclear accumulation and target gene expression, and silencing SREBP impairs lipogenesis and reduces cell size in vitro and in flies, indicating that the PI3K/Akt/mTOR pathway coordinates protein and lipid biosynthesis for cell growth.

Abstract

Cell growth (accumulation of mass) needs to be coordinated with metabolic processes that are required for the synthesis of macromolecules. The PI3-kinase/Akt signaling pathway induces cell growth via activation of complex 1 of the target of rapamycin (TORC1). Here we show that Akt-dependent lipogenesis requires mTORC1 activity. Furthermore, nuclear accumulation of the mature form of the sterol responsive element binding protein (SREBP1) and expression of SREBP target genes was blocked by the mTORC1 inhibitor rapamycin. We also show that silencing of SREBP blocks Akt-dependent lipogenesis and attenuates the increase in cell size in response to Akt activation in vitro. Silencing of dSREBP in flies caused a reduction in cell and organ size and blocked the induction of cell growth by dPI3K. Our results suggest that the PI3K/Akt/TOR pathway regulates protein and lipid biosynthesis in an orchestrated manner and that both processes are required for cell growth.