Mechanism of Activation of AMPK and Upregulation of OGG1 by Rapamycin in Cancer Cells

AMPK is a physiological cellular energy sensor that is activated by phosphorylation at Thr172 in response to changes in cellular ATP levels. AMPK has been recognized as an important upstream signaling intermediate intimately involved in the regulation of the mTOR pathway [1]. AMPK responds to energy stress by suppressing cell growth and biosynthetic processes, in part through its inhibition of the rapamycin-sensitive mTOR (mTORC1) pathway. In addition, AMPK directly phosphorylates the mTOR binding partner raptor on two well-conserved serine residues, and this phosphorylation induces 14-3-3 binding to raptor. The phosphorylation of raptor by AMPK is required for the inhibition of mTORC1 and cell cycle arrest induced by energy stress. Recent studies show that raptor was identified as