Fig. 1.

mTOR regulation pathway involved in hypoxia. Everolimus combines with FKBP12, and obstructs the function of mTOR. p-mTOR (phosphorylated-mTOR) is inhibited by everolimus. Inhibition of mTOR increases the binding of 4E-BP1 to elF-4E, consequently leading to inactivation of HIF-1α mRNA translation. HIF-1 composed of α unit and β unit binds to hypoxia response elements (HREs), resulting in the upregulation of hypoxia-related factors such as VEGF (vascular endothelial growth factor), GLUT-1 (glucose transporter-1), and EPO (erythropoietin).