P53/TAp63 and AKT regulate mammalian target of rapamycin complex 1 (mTORC1) signaling through two independent parallel pathways in the presence of DNA damage

Background: mTORC1 integrates cellular inputs and is often deregulated in cancer. Results: In response to DNA damage, p53/TAp63 and AKT regulate mTORC1 through two independent parallel pathways. Conclusion: DNA damage activates Akt, resulting in inhibition of S6K1, whereas Sestrin1/2 downstream of p53 and REDD1 downstream of p63 coordinate to suppress 4E-BP1. Significance: mTORC1-dependent 4EBP1 inhibition by DNA damage is abrogated in most human cancers.