title: The regulation of energy metabolism and the IGF-1/mTOR pathways by the p53 protein.
abstract: In response to stress, p53 initiates the transcriptional regulation of selected target genes and various cellular responses, including cell cycle arrest, apoptosis and senescence. Recent studies revealed two additional functions of p53 in the regulation of IGF-1/AKT/mTOR pathways and energy metabolism, contributing to p53's role as a tumor suppressor. Oncogenic processes give rise to metabolic pathways focused upon the use of aerobic glycolysis (the Warburg effect) and the pentose shunt, providing higher levels of reducing activities. p53 shuts down these pathways and refocuses cells to utilize mitochondrial oxidative phosphorylation, thereby maximizing efficient ATP production and minimizing the synthesis of substrates for cell division. The use of these alternative metabolic pathways is an integral part of both normal and oncogenic phenotypes.
authors.affiliation: Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA. fengzh@umdnj.edu
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Feng
authors.forename: Arnold J
authors.initials: AJ
authors.lastname: Levine
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D058570:TOR Serine-Threonine Kinases; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D016159:Tumor Suppressor Protein p53; D007334:Insulin-Like Growth Factor I; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases
references.citation: Science. 2004 Apr 23;304(5670):596-600
references.pmid: 15105503
references.citation: Cell. 2009 May 1;137(3):413-31
references.pmid: 19410540
references.citation: Cell. 2002 Jul 26;110(2):177-89
references.pmid: 12150926
references.citation: Cell. 2008 Aug 8;134(3):451-60
references.pmid: 18692468
references.citation: Mol Cell. 2008 May 9;30(3):263-5
references.pmid: 18471972
references.citation: Nat Cell Biol. 2001 Nov;3(11):973-82
references.pmid: 11715018
references.citation: J Biol Chem. 2005 Sep 23;280(38):33076-82
references.pmid: 16049009
references.citation: J Hum Genet. 2004;49(3):134-140
references.pmid: 14986171
references.citation: Curr Biol. 2004 Jul 27;14(14):1296-302
references.pmid: 15268862
references.citation: Nat Rev Cancer. 2003 Oct;3(10):721-32
references.pmid: 13130303
references.citation: Biochem Biophys Res Commun. 2001 Sep 21;287(2):562-7
references.pmid: 11554766
references.citation: Science. 2006 Jun 16;312(5780):1650-3
references.pmid: 16728594
references.citation: Genes Dev. 2004 Dec 1;18(23):2893-904
references.pmid: 15545625
references.citation: Nature. 2009 Aug 27;460(7259):1149-53
references.pmid: 19668189
references.citation: Cell. 2006 Oct 6;127(1):125-37
references.pmid: 16962653
references.citation: J Carcinog. 2009;8:8
references.pmid: 19439913
references.citation: Cell. 2008 Sep 5;134(5):703-7
references.pmid: 18775299
references.citation: Cell Death Differ. 2009 Aug;16(8):1135-45
references.pmid: 19300452
references.citation: Science. 2004 Oct 22;306(5696):695-8
references.pmid: 15499020
references.citation: Cancer Res. 2005 Jan 1;65(1):177-85
references.pmid: 15665293
references.citation: Nature. 2006 May 25;441(7092):424-30
references.pmid: 16724053
references.citation: Mol Cell. 2003 Apr;11(4):895-904
references.pmid: 12718876
references.citation: Nat Rev Cancer. 2009 Aug;9(8):550-62
references.pmid: 19629070
references.citation: Cancer Res. 2006 May 1;66(9):4795-801
references.pmid: 16651434
references.citation: Science. 2006 May 26;312(5777):1158-9
references.pmid: 16728625
references.citation: Cell. 2008 Jan 11;132(1):27-42
references.pmid: 18191218
references.citation: Nat Rev Cancer. 2004 Nov;4(11):891-9
references.pmid: 15516961
references.citation: Nature. 2008 Mar 13;452(7184):230-3
references.pmid: 18337823
references.citation: Cell Death Differ. 2006 Jun;13(6):1027-36
references.pmid: 16557269
references.citation: Cancer Res. 2004 Jun 1;64(11):3892-9
references.pmid: 15172999
references.citation: Nat Cell Biol. 2004 Nov;6(11):1122-8
references.pmid: 15467718
references.citation: Curr Opin Cell Biol. 2006 Dec;18(6):598-608
references.pmid: 17046224
references.citation: Cancer Res. 2007 Apr 1;67(7):3043-53
references.pmid: 17409411
references.citation: Nature. 2000 Mar 2;404(6773):42-9
references.pmid: 10716435
references.citation: Mol Cell. 2001 Aug;8(2):317-25
references.pmid: 11545734
references.citation: Nature. 2009 Aug 27;460(7259):1145-8
references.pmid: 19668190
references.citation: Nat Genet. 2007 Jun;39(6):776-80
references.pmid: 17486094
references.citation: Oncogene. 2005 Nov 14;24(50):7435-42
references.pmid: 16288290
references.citation: Cancer Cell. 2004 Jul;6(1):91-9
references.pmid: 15261145
references.citation: Curr Opin Cell Biol. 2005 Dec;17(6):596-603
references.pmid: 16226444
references.citation: Nature. 2009 Aug 27;460(7259):1132-5
references.pmid: 19668191
references.citation: Nature. 2008 Feb 28;451(7182):1069-75
references.pmid: 18305538
references.citation: Mol Cell. 2005 Apr 15;18(2):143-5
references.pmid: 15837416
references.citation: Mol Cell Biol. 2009 Nov;29(21):5645-56
references.pmid: 19704005
references.citation: Nat Cell Biol. 2008 May;10(5):611-8
references.pmid: 18391940
references.citation: Nat Rev Cancer. 2006 Mar;6(3):184-92
references.pmid: 16453012
references.citation: Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):424-8
references.pmid: 9892649
references.citation: Mol Cell Biol. 2003 Dec;23(23):8862-77
references.pmid: 14612424
references.citation: Mol Cell Biol. 2002 Sep;22(17):6247-60
references.pmid: 12167717
references.citation: EMBO J. 2007 Nov 28;26(23):4812-23
references.pmid: 17962806
references.citation: Genes Dev. 2006 Feb 1;20(3):267-75
references.pmid: 16452501
references.citation: Nat Rev Cancer. 2005 Dec;5(12):921-9
references.pmid: 16341083
references.citation: Cell. 2002 Jul 26;110(2):163-75
references.pmid: 12150925
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 16;106(24):9761-6
references.pmid: 19470478
references.citation: Cell Metab. 2006 Mar;3(3):187-97
references.pmid: 16517406
references.citation: Cancer Res. 2004 Apr 1;64(7):2627-33
references.pmid: 15059920
references.citation: FEBS J. 2009 Apr;276(8):2201-12
references.pmid: 19302216
references.citation: Nat Cell Biol. 2006 Jul;8(7):688-99
references.pmid: 16799551
references.citation: Cell. 2004 Jan 23;116(2 Suppl):S67-9, 1 p following S69
references.pmid: 15055586
references.citation: J Biol Chem. 2005 Jul 15;280(28):26089-93
references.pmid: 15905173
references.citation: Nat Cell Biol. 2002 Sep;4(9):648-57
references.pmid: 12172553
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8204-9
references.pmid: 15928081
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15077-82
references.pmid: 14657337
references.citation: Neuron. 2005 Jul 7;47(1):29-41
references.pmid: 15996546
references.citation: J Biol Chem. 1999 Apr 23;274(17):12061-6
references.pmid: 10207030
references.citation: Cell Cycle. 2008 Oct;7(19):3056-61
references.pmid: 18818522
references.citation: Cell. 2003 Nov 26;115(5):577-90
references.pmid: 14651849
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7455-60
references.pmid: 20378837
references.citation: Cell Metab. 2006 Mar;3(3):177-85
references.pmid: 16517405
references.citation: Cell. 2005 Jan 28;120(2):237-48
references.pmid: 15680329
references.citation: Cell Metab. 2005 Jan;1(1):15-25
references.pmid: 16054041
references.citation: Oncogene. 2006 Jan 5;25(1):1-7
references.pmid: 16278683
references.citation: Cell. 2006 Jul 14;126(1):121-34
references.pmid: 16839881
references.citation: Cell. 2005 Nov 18;123(4):569-80
references.pmid: 16286006
references.citation: Science. 2005 Feb 18;307(5712):1098-101
references.pmid: 15718470
references.citation: Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6658-63
references.pmid: 9192621
references.citation: Mol Cell. 2002 Nov;10(5):995-1005
references.pmid: 12453409
references.citation: Nature. 2007 Nov 29;450(7170):721-4
references.pmid: 18046411
references.citation: Cell. 2006 Jul 14;126(1):107-20
references.pmid: 16839880
references.citation: Mol Cell. 2005 Apr 29;18(3):283-93
references.pmid: 15866171
references.citation: Science. 1956 Feb 24;123(3191):309-14
references.pmid: 13298683
references.citation: Cancer Cell. 2006 Jun;9(6):425-34
references.pmid: 16766262