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 Weintraub; Tyler Curiel; Z. Dave Sharp; Paul Hasty

doi:10.18632/oncotarget.4602

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 Weintraub, Tyler Curiel, Z. Dave Sharp, Paul Hasty

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

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 language	English (US)
Pages (from-to)	15802-15813
Number of pages	12
Journal	Oncotarget
Volume	6
Issue number	18
DOIs	https://doi.org/10.18632/oncotarget.4602
State	Published - 2015

Keywords

Longevity
Rapamycin
SASP
mTOR
p53

ASJC Scopus subject areas

Oncology

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10.18632/oncotarget.4602

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title = "P53 and rapamycin are additive",

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.",

keywords = "Longevity, Rapamycin, SASP, mTOR, p53",

author = "Barbara Christy and Marco Demaria and Judith Campisi and Jing Huang and Diane Jones and Dodds, {Sherry G.} and Charnae Williams and Gene Hubbard and Livi, {Carolina B.} and Xiaoli Gao and Susan Weintraub and Tyler Curiel and Sharp, {Z. Dave} and Paul Hasty",

year = "2015",

doi = "10.18632/oncotarget.4602",

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TY - JOUR

T1 - P53 and rapamycin are additive

AU - Christy, Barbara

AU - Demaria, Marco

AU - Campisi, Judith

AU - Huang, Jing

AU - Jones, Diane

AU - Dodds, Sherry G.

AU - Williams, Charnae

AU - Hubbard, Gene

AU - Livi, Carolina B.

AU - Gao, Xiaoli

AU - Weintraub, Susan

AU - Curiel, Tyler

AU - Sharp, Z. Dave

AU - Hasty, Paul

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - Longevity

KW - Rapamycin

KW - SASP

KW - mTOR

KW - p53

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DO - 10.18632/oncotarget.4602

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SN - 1949-2553

VL - 6

SP - 15802

EP - 15813

JO - Oncotarget

JF - Oncotarget

IS - 18

ER -

P53 and rapamycin are additive

Abstract

Keywords

ASJC Scopus subject areas

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