The human ΔNp53 isoform triggers metabolic and gene expression changes that activate mTOR and alter mitochondrial function

Aging Cell

Volumn 12, Issue 5, 2013, Pages 863-872

  Lin, Shih Chieh ^a   Karoly, Edward D ^b   Taatjes, Dylan J ^a  

^a UNIVERSITY OF COLORADO   (United States)

^b METABOLON INC   (United States)

Author keywords

2HG; DOT1L; Epigenetic; Glutathione; Polyamines; Urea cycle

Indexed keywords

2 HYDROXYGLUTARIC ACID; ACETYL COENZYME A; ADENOSINE TRIPHOSPHATE; AMINO ACID; CARNITINE; INSULIN RECEPTOR SUBSTRATE 1; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN DELTA NP53; PROTEIN P53; SUCCINIC ACID; TETRAMER; UNCLASSIFIED DRUG;

AGING; ARTICLE; CITRIC ACID CYCLE; CONTROLLED STUDY; ENZYME ACTIVATION; EPIGENETICS; GENE EXPRESSION REGULATION; GENETIC TRANSCRIPTION; IN VITRO STUDY; METABOLIC REGULATION; MICROARRAY ANALYSIS; MITOCHONDRION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN STABILITY; PROTEIN STRUCTURE; SIGNAL TRANSDUCTION; WILD TYPE;

MUS;

2HG; DOT1L; EPIGENETIC; GLUTATHIONE; POLYAMINES; UREA CYCLE;

AGE FACTORS; AMINO ACID SEQUENCE; EPIGENOMICS; GENE EXPRESSION REGULATION; GENES, P53; GLUTATHIONE; HUMANS; MITOCHONDRIA; MOLECULAR SEQUENCE DATA; PROTEIN ISOFORMS; PROTEIN STRUCTURE, TERTIARY; TOR SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84883827546     PISSN: 14749718     EISSN: 14749726     Source Type: Journal    
DOI: 10.1111/acel.12108     Document Type: Article

References (39)

1. Bahar R, Hartmann CH, Rodriguez KA, Denny AD, Busuttil RA, Dolle ME, Calder RB, Chisholm GB, Pollock BH, Klein CA, Vijg J (2006) Increased cell-to-cell variation in gene expression in ageing mouse heart. Nature 441, 1011-1014.
2. Baran CP, Tridandapani S, Helgason CD, Humphries RK, Krystal G, Marsh CB (2003) The inositol 5′-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity. J. Biol. Chem. 278, 38628-38636.
3. Bayat V, Thiffault I, Jaiswal M, Tetreault M, Donti T, Sasarman F, Bernard G, Demers-Lamarche J, Dicaire MJ, Mathieu J, Vanasse M, Bouchard JP, Rioux MF, Lourenco CM, Li Z, Haueter C, Shoubridge EA, Graham BH, Brais B, Bellen HJ (2012) Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative Phenotype in flies and a recessive ataxia (ARSAL) in humans. PLoS Biol. 10, e1001288.
4. Bonasio R, Tu S, Reinberg D (2010) Molecular signals of epigenetic states. Science 330, 612-616.
5. Bourougaa K, Naski N, Boularan C, Mlynarczyk C, Candeias MM, Marullo S, Fahraeus R (2010) Endoplasmic reticulum stress induces G2 cell-cycle arrest via mRNA translation of the p53 isoform p53/47. Mol. Cell 38, 78-88.
6. Candeias MM, Powell DJ, Roubalova E, Apcher S, Bourougaa K, Vojtesek B, Bruzzoni-Giovanelli H, Fahraeus R (2006) Expression of p53 and p53/47 are controlled by alternative mechanisms of messenger RNA translation initiation. Oncogene 25, 6936-6947.
7. Courtois S, Verhaegh G, North S, Luciani MG, Lassus P, Hibner U, Oren M, Hainaut P (2002) DeltaN-p53, a natural isoform of p53 lacking the first transactivation domain, counteracts growth suppression by wild-type p53. Oncogene 21, 6722-6728.
8. Espinosa JM (2008) Mechanisms of regulatory diversity within the p53 transcriptional network. Oncogene 27, 4013-4023.
9. Feng Z, Levine AJ (2010) The regulation of energy metabolism and the IGF-1/mTOR pathways by the p53 protein. Trends Cell Biol. 20, 427-434.
10. Freed-Pastor WA, Prives C (2012) Mutant p53: one name, many proteins. Genes Dev. 26, 1268-1286.
11. Gardai S, Whitlock BB, Helgason C, Ambruso D, Fadok V, Bratton D, Henson PM (2002) Activation of SHIP by NADPH oxidase-stimulated Lyn leads to enhanced apoptosis in neutrophils. J. Biol. Chem. 277, 5236-5246.
12. Knuesel MT, Meyer KD, Bernecky C, Taatjes DJ (2009) The human CDK8 subcomplex is a molecular switch that controls Mediator co-activator function. Genes Dev. 23, 439-451.
13. Kumar C, Igbaria A, D'Autreaux B, Planson AG, Junot C, Godat E, Bachhawat AK, Delaunay-Moisan A, Toledano MB (2011) Glutathione revisited: a vital function in iron metabolism and ancillary role in thiol-redox control. EMBO J. 30, 2044-2056.
14. Laplante M, Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149, 274-293.
15. Lawton KA, Berger A, Mitchell M, Milgram KE, Evans AM, Guo L, Hanson RW, Kalhan SC, Ryals JA, Milburn MV (2008) Analysis of the adult human plasma metabolome. Pharmacogenomics 9, 383-397.
16. Lill R (2009) Function and biogenesis of iron-sulphur proteins. Nature 460, 831-838.
17. Maier B, Gluba W, Bernier B, Turner T, Mohammad K, Guise T, Sutherland A, Thorner M, Scrable H (2004) Modulation of mammalian life span by the short isoform of p53. Genes Dev. 18, 306-319.
18. Marshall L, Kenneth NS, White RJ (2008) Elevated tRNA(iMet) synthesis can drive cell proliferation and oncogenic transformation. Cell 133, 78-89.
19. Martin GM (2009) Epigenetic gambling and epigenetic drift as an antagonistic pleiotropic mechanism of aging. Aging Cell 8, 761-764.
20. Nicholls CD, McLure KG, Shields MA, Lee PW (2002) Biogenesis of p53 involves cotranslational dimerization of monomers and posttranslational dimerization of dimers. Implications on the dominant negative effect. J. Biol. Chem. 277, 12937-12945.
21. Okorokov AL, Sherman MB, Plisson C, Grinkevich V, Sigmundsson K, Selivanova G, Milner J, Orlova EV (2006) The structure of p53 tumor suppressor protein reveals the basis for its functional plasticity. EMBO J. 25, 5191-5200.
22. Pehar M, O'Riordan KJ, Burns-Cusato M, Andrzejewski ME, del Alcazar CG, Burger C, Scrable H, Puglielli L (2010) Altered longevity-assurance activity of p53:p44 in the mouse causes memory loss, neurodegeneration and premature death. Aging Cell 9, 174-190.
23. Powell DJ, Hrstka R, Candeias M, Bourougaa K, Vojtesek B, Fahraeus R (2008) Stress-dependent changes in the properties of p53 complexes by the alternative translation product p53/47. Cell Cycle 7, 950-959.
24. Ray PS, Grover R, Das S (2006) Two internal ribosome entry sites mediate the translation of p53 isoforms. EMBO Rep. 7, 404-410.
25. Reitman ZJ, Jin G, Karoly ED, Spasojevic I, Yang J, Kinzler KW, He Y, Bigner DD, Vogelstein B, Yan H (2011) Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome. Proc. Natl. Acad. Sci. U. S. A. 108, 3270-3275.
26. Sasaki M, Knobbe CB, Itsumi M, Elia AJ, Harris IS, Chio II, Cairns RA, McCracken S, Wakeham A, Haight J, Ten AY, Snow B, Ueda T, Inoue S, Yamamoto K, Ko M, Rao A, Yen KE, Su SM, Mak TW (2012) D-2-hydroxyglutarate produced by mutant IDH1 perturbs collagen maturation and basement membrane function. Genes Dev. 26, 2038-2049.
27. Shin SC, Kim SH, You H, Kim B, Kim AC, Lee KA, Yoon JH, Ryu JH, Lee WJ (2011) Drosophila microbiome modulates host developmental and metabolic homeostasis via insulin signaling. Science 334, 670-674.
28. Somel M, Khaitovich P, Bahn S, Paabo S, Lachmann M (2006) Gene expression becomes heterogeneous with age. Curr. Biol. 16, R359-R360.
29. Tyner SD, Venkatachalam S, Choi J, Jones S, Ghebranious N, Igelmann H, Lu X, Soron G, Cooper B, Brayton C, Park SH, Thompson T, Karsenty G, Bradley A, Donehower LA (2002) p53 mutant mice that display early ageing-associated phenotypes. Nature 415, 45-53.
30. Ungewitter E, Scrable H (2010) Delta40p53 controls the switch from pluripotency to differentiation by regulating IGF signaling in ESCs. Genes Dev. 24, 2408-2419.
31. Vendelbo MH, Nair KS (2011) Mitochondrial longevity pathways. Biochim. Biophys. Acta 1813, 634-644.
32. Vijg J, Campisi J (2008) Puzzles, promises and a cure for ageing. Nature 454, 1065-1071.
33. Vousden KH, Ryan KM (2009) p53 and metabolism. Nat. Rev. Cancer 9, 691-700.
34. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 57-63.
35. Wishart DS, Knox C, Guo AC, Eisner R, Young N, Gautam B, Hau DD, Psychogios N, Dong E, Bouatra S, Mandal R, Sinelnikov I, Xia J, Jia L, Cruz JA, Lim E, Sobsey CA, Shrivastava S, Huang P, Liu P, Fang L, Peng J, Fradette R, Cheng D, Tzur D, Clements M, Lewis A, De Souza A, Zuniga A, Dawe M, Xiong Y, Clive D, Greiner R, Nazyrova A, Shaykhutdinov R, Li L, Vogel HJ, Forsythe I (2009) HMDB: a knowledgebase for the human metabolome. Nucleic Acids Res. 37, D603-D610.
36. Xiao M, Yang H, Xu W, Ma S, Lin H, Zhu H, Liu L, Liu Y, Yang C, Xu Y, Zhao S, Ye D, Xiong Y, Guan KL (2012) Inhibition of alpha-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes Dev. 26, 1326-1338.
37. Xu J, Marzetti E, Seo AY, Kim JS, Prolla TA, Leeuwenburgh C (2010) The emerging role of iron dyshomeostasis in the mitochondrial decay of aging. Mech. Ageing Dev. 131, 487-493.
38. Xu W, Yang H, Liu Y, Yang Y, Wang P, Kim SH, Ito S, Yang C, Wang P, Xiao MT, Liu LX, Jiang WQ, Liu J, Zhang JY, Wang B, Frye S, Zhang Y, Xu YH, Lei QY, Guan KL, Zhao SM, Xiong Y (2011) Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell 19, 17-30.
39. Zahn JM, Poosala S, Owen AB, Ingram DK, Lustig A, Carter A, Weeraratna AT, Taub DD, Gorospe M, Mazan-Mamczarz K, Lakatta EG, Boheler KR, Xu X, Mattson MP, Falco G, Ko MS, Schlessinger D, Firman J, Kummerfeld SK, Wood WH 3rd, Zonderman AB, Kim SK, Becker KG (2007) AGEMAP: a gene expression database for aging in mice. PLoS Genet. 3, e201.