P53 and rapamycin are additive

Barbara Christy, Marco Demaria, Judith Campisi, Jing Huang, Diane Jones, Sherry G. Dodds, Charnae Williams, Gene Hubbard, Carolina B. Livi, Xiaoli Gao, Susan E Weintraub, Tyler J Curiel, Zelton D Sharp, Edward P Hasty

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 (US)
Pages (from-to)15802-15813
Number of pages12
JournalOncotarget
Volume6
Issue number18
StatePublished - 2015

Fingerprint

Sirolimus
Tacrolimus Binding Proteins
Amino Acids
Ionizing Radiation
Citric Acid
Neoplasms
Phosphotransferases
Phenotype
Growth
mechanistic target of rapamycin complex 1

Keywords

  • Longevity
  • mTOR
  • p53
  • Rapamycin
  • SASP

ASJC Scopus subject areas

  • Oncology

Cite this

Christy, B., Demaria, M., Campisi, J., Huang, J., Jones, D., Dodds, S. G., ... Hasty, E. P. (2015). P53 and rapamycin are additive. Oncotarget, 6(18), 15802-15813.

P53 and rapamycin are additive. / Christy, Barbara; Demaria, Marco; Campisi, Judith; Huang, Jing; Jones, Diane; Dodds, Sherry G.; Williams, Charnae; Hubbard, Gene; Livi, Carolina B.; Gao, Xiaoli; Weintraub, Susan E; Curiel, Tyler J; Sharp, Zelton D; Hasty, Edward P.

In: Oncotarget, Vol. 6, No. 18, 2015, p. 15802-15813.

Research output: Contribution to journalArticle

Christy, B, Demaria, M, Campisi, J, Huang, J, Jones, D, Dodds, SG, Williams, C, Hubbard, G, Livi, CB, Gao, X, Weintraub, SE, Curiel, TJ, Sharp, ZD & Hasty, EP 2015, 'P53 and rapamycin are additive', Oncotarget, vol. 6, no. 18, pp. 15802-15813.
Christy B, Demaria M, Campisi J, Huang J, Jones D, Dodds SG et al. P53 and rapamycin are additive. Oncotarget. 2015;6(18):15802-15813.
Christy, Barbara ; Demaria, Marco ; Campisi, Judith ; Huang, Jing ; Jones, Diane ; Dodds, Sherry G. ; Williams, Charnae ; Hubbard, Gene ; Livi, Carolina B. ; Gao, Xiaoli ; Weintraub, Susan E ; Curiel, Tyler J ; Sharp, Zelton D ; Hasty, Edward P. / P53 and rapamycin are additive. In: Oncotarget. 2015 ; Vol. 6, No. 18. pp. 15802-15813.
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