Publication

p53 and rapamycin are additive

Christy, B., Demaria, M., Campisi, J., Huang, J., Jones, D., Dodds, S. G., Williams, C., Hubbard, G., Livi, C. B., Gao, X., Weintraub, S., Curiel, T., Sharp, Z. D. & Hasty, P., 30-Jun-2015, In : Oncotarget. 6, 18, p. 15802-13 12 p.

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DOI

  • Barbara Christy
  • Marco Demaria
  • Judith Campisi
  • Jing Huang
  • Diane Jones
  • Sherry G Dodds
  • Charnae Williams
  • Gene Hubbard
  • Carolina B Livi
  • Xiaoli Gao
  • Susan Weintraub
  • Tyler Curiel
  • Z Dave Sharp
  • Paul Hasty

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.

Original languageEnglish
Pages (from-to)15802-13
Number of pages12
JournalOncotarget
Volume6
Issue number18
Publication statusPublished - 30-Jun-2015
Externally publishedYes

    Keywords

  • EXTENDS LIFE-SPAN, CELL-CYCLE ARREST, GENETICALLY HETEROGENEOUS MICE, EMBRYONIC STEM-CELLS, DNA-DAMAGE RESPONSE, TUMOR SUPPRESSION, DIETARY-RESTRICTION, TRANSPLANT RECIPIENTS, MAINTENANCE PATHWAYS, SECRETORY PHENOTYPE

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