Schematic representation and overview of PTEN/PI3K/AKT signaling and amodel of the mechanism of peroxisome proliferator-activated receptor(PPAR) action. Similar to other nuclear hormone receptors, PPARsact as a ligand-activated transcription factor. PPARs, in response toligand binding, hetero-dimerize with retinoid-X-receptor (RXR) and bindPPAR response element (PPRE) DNA sequences in the promoters of targetgenes, including PTEN. The uncontrolled generation of reactiveoxygen species (ROS) might contribute to cell proliferation byinhibiting PTEN function. Examples of molecules known to act on thePTEN/PI3K/AKT regulatory pathways are also shown; these molecules mayrelate to the function of presenilin. Hammerheads mean inhibition. Somecritical pathways have been omitted for clarity. GSK3, glycogen synthasekinase-3; HDM2, human homologue of murine mdm2; HIF-1α,hypoxia-inducible factor-1α; IKK, IκB kinase; MAPK,mitogen-activated protein kinase; mTOR, mammalian target of rapamycin;NF-κB, nuclear factor-kappa-B; NOS, nitric oxide synthase; PI3K,phosphoinositide-3 kinase; PTEN, phosphatase and tensin homologuedeleted on chromosome 10; PUFA, polyunsaturated fatty acid; RA, retinoicacid; TSC, tuberous sclerosis complex; TSP1, thrombospondin 1; VEGF,vascular endothelial growth factor.