Journal
ONCOTARGET
Volume 6, Issue 18, Pages 15802-15813Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4602
Keywords
mTOR; p53; rapamycin; longevity; SASP
Categories
Funding
- NIH [RC2AG036613]
- [P01AG017242]
- [1S10RR031586-01]
- [P30 CA054174]
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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.
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