p53 and rapamycin are additive

• Published in: Oncotarget Vol. 6; no. 18; pp. 15802 - 15813
• Main Authors: Christy, Barbara, Demaria, Marco, Campisi, Judith, Huang, Jing, Jones, Diane, Dodds, Sherry G, Williams, Charnae, Hubbard, Gene, Livi, Carolina B, Gao, Xiaoli, Weintraub, Susan, Curiel, Tyler, Sharp, Z Dave, Hasty, Paul
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 30-06-2015
• Subjects: Animals; Cell Line; Cell Proliferation; Embryonic Stem Cells - drug effects; Embryonic Stem Cells - metabolism; Female; Fibroblasts; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Priority Research Paper; Signal Transduction; Sirolimus - blood; Sirolimus - metabolism; Sirolimus - pharmacology; TOR Serine-Threonine Kinases - metabolism; Tumor Suppressor Protein p53 - biosynthesis; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; mTOR; longevity; SASP; p53; rapamycin
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.4602

Mechanistic target of rapamycin (mTOR) is a kinase found in a complex (mTORC1) that enables macromolecular synthesis and cell growth and is implicated in cancer etiology. The rapamycin-FK506 binding protein 12 (FKBP12) complex allosterically inhibits mTORC1. In response to stress, p53 inhibits mTORC1 through a separate pathway involving cell signaling and amino acid sensing. Thus, these different mechanisms could be additive. Here we show that p53 improved the ability of rapamycin to: 1) extend mouse life span, 2) suppress ionizing radiation (IR)-induced senescence-associated secretory phenotype (SASP) and 3) increase the levels of amino acids and citric acid in mouse embryonic stem (ES) cells. This additive effect could have implications for cancer treatment since rapamycin and p53 are anti-oncogenic.