Editorial Volume 2, Issue 7 pp 380—382

Figure 1. Signaling circuitry connecting Mdm2 with the regulation of longevity and metabolism. Both mTORC1 and 2 (mammalian target of rapamycin complex 1/2) are able to positively regulate the activity of Mdm2, either through enhancement of translation of Mdm2 mRNA or via activation of AKT. Conversely, Mdm2 can activate mTORC1 by targeting p53 for degradation. p53 negatively regulates mTORC1 by activating TSC1/2 (tuberous sclerosis 1/2) complex, which acts as a GTPase activating protein (GAP) for Rheb (Ras homologue enriched in brain). p53 can also repress the activity of PI-3K (phosphatidylinositol 3-kinase) by induction of PTEN (phosphatase and tensin homologue), leading to further downregulation of mTORC1. Arrows represent up-regulation. Orange diamonds represent kinase activity. Blue diamonds represent E3 ubiquitin ligase activity of Mdm2. AMPK, AMP-activated protein kinase; FOXO, Forkhead box; PDK1, 3-phosphoinositide-dependent protein kinase 1.