<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">rsp</journal-id><journal-title-group><journal-title xml:lang="ru">Научно-практическая ревматология</journal-title><trans-title-group xml:lang="en"><trans-title>Rheumatology Science and Practice</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1995-4484</issn><issn pub-type="epub">1995-4492</issn><publisher><publisher-name>IMA-PRESS, LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.14412/1995-4484-2010-444</article-id><article-id custom-type="elpub" pub-id-type="custom">rsp-582</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>Статьи</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>Articles</subject></subj-group></article-categories><title-group><article-title>Белок р-53: новая жизнь старой молекулы. Часть I</article-title><trans-title-group xml:lang="en"><trans-title>Belok r-53: novaya zhizn' staroy molekuly. Chast' I</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Дубиков</surname><given-names>А. И.</given-names></name><name name-style="western" xml:lang="en"><surname>Dubikov</surname><given-names>Alecsandr Ivanovich</given-names></name></name-alternatives><email xlink:type="simple">aihavlad@online.vladivostok.ru</email></contrib></contrib-group><pub-date pub-type="collection"><year>2010</year></pub-date><pub-date pub-type="epub"><day>15</day><month>06</month><year>2010</year></pub-date><volume>48</volume><issue>3</issue><issue-title>№3 (2010)</issue-title><fpage>52</fpage><lpage>58</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Дубиков А.И., 2010</copyright-statement><copyright-year>2010</copyright-year><copyright-holder xml:lang="ru">Дубиков А.И.</copyright-holder><copyright-holder xml:lang="en">Dubikov A.I.</copyright-holder><license license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://rsp.mediar-press.net/rsp/article/view/582">https://rsp.mediar-press.net/rsp/article/view/582</self-uri></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">&lt;div&gt;&lt;p&gt;Firestein G.S., Echeverri F., Yeo M. et al. Somatic mutations in the p53 tumor suppressor gene in rheumatoid arthritis synovium. Proc Natl Acad Sci USA 1997;94:10895-900.&lt;/p&gt;&lt;p&gt;Yamanishi Y., Boyle D.L., Rosengren S. et al. Regional analysis of p53 mutations in rheumatoid arthritis synovium. Proc Natl Acad Sci USA 2002;99:10025-30.&lt;/p&gt;&lt;p&gt;Pap T., Aupperle K.R., Gay S. Invasiveness of synovial fibroblasts is regulated by p53 in the SCID mouse in vivo model of cartilage invasion. Arthr Rheum 2001;44:676-81.&lt;/p&gt;&lt;p&gt;Yao Q., Wang S., Glorioso J.C. et al. Gene transfer of p53 to arthritic joints stimulates synovial apoptosis and inhibits inflammation. Mol Theor 2001;3:901-10.&lt;/p&gt;&lt;p&gt;Yamanishi Y., Boyle D.L., Pinkoski M.J. et al. Regulation of joint destruction and inflammation by p53 in collagen-induced arthritis. Am J Pathol 2002;160:123-30.&lt;/p&gt;&lt;p&gt;Leech M., Xue J.R., Dacumos A. et al. The tumour suppressor gene p53 modulates the severity of antigen-induced arthritis and the systemic immune response. Clin Exp Immunol 2008;152(2):345-53.&lt;/p&gt;&lt;p&gt;Yu J., Zhang L. No PUMA, no death: implications for p53-dependent apoptosis. Cancer Cell 2003;4:248-9.&lt;/p&gt;&lt;p&gt;Michalak E.M., Villunger A., Adams J.M., Strasser A. In several cell types tumour suppressor p53 induces apoptosis largely via Puma but Noxa can contribute. Cell Death Differ 2008;15:1019-29.&lt;/p&gt;&lt;p&gt;Garrison S.P., Jeffers J.R., Yang C. et al. Selection against PUMA gene expression in Myc-driven B cell lymphomagenesis. Mol Cell Biol 2008;28:5391-402.&lt;/p&gt;&lt;p&gt;Hemann M.T., Zilfou J.T., Zhao Z. et al. Suppression of tumorigenesis by the p53 target PUMA. Proc Natl Acad Sci USA 2004;101:9333-8.&lt;/p&gt;&lt;p&gt;Rowan S., Ludwig R.L., Haupt Y. et al. Specific loss of apoptotic but not cell cycle arrest function in a human tumour derived p53 mutant. EMBO J 1996;15:827-38.&lt;/p&gt;&lt;p&gt;Liu G., Parant J.M., Lang G. et al. Chromosomal stability, in the absence of apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice. Nat Genet 2004;36:63-8.&lt;/p&gt;&lt;p&gt;El-Deiry W.S. Regulation of p53 downstream genes. Semin. Cancer Biol 1998;8:345-57.&lt;/p&gt;&lt;p&gt;Deng Y., Chan S.S., Chang S. Telomere dysfunction and tumour suppression: the senescence connection. Nat Rev Cancer 2008;8:450-8.&lt;/p&gt;&lt;p&gt;Halazonetis T.D., Gorgoulis V.G.,Barteck J. An oncogene-induced DNA damage model for cancer development. Science 2008;319:1352-5.&lt;/p&gt;&lt;p&gt;Martins C.P., Brown-Swigart L., Evan G.I. Modeling the therapeutic efficacy of p53 restoration in tumors. Cell 2006;127:1323-34.&lt;/p&gt;&lt;p&gt;Ventura A., Kirsch D.G., McLaughlin M.E. et al. Restoration of p53 function leads to tumour regression in vivo. Nature 2007;445:661-5.&lt;/p&gt;&lt;p&gt;Xue W., Zender L., Miething C. et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007;445:656-60.&lt;/p&gt;&lt;p&gt;Brown J.P., Wei W., Sedivy J.M. Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science 1997;277:831-4.&lt;/p&gt;&lt;p&gt;Cosme-Blanco W., Shen M.-F., Lazar A.J.F. et al. Telomere dysfunction suppresses spontaneous tumorigeesis in vivo by initiating p53-dependent cellular senescence. EMBO Rep 2007;8:497-503&lt;/p&gt;&lt;p&gt;Van Nguyen T., Puebla-Osorio N., Pang H. et al. DNA damage-induced cellular senescence is sufficient to suppress tumorigenesis: a mouse model. J Exp Med 2007;204:1453-61.&lt;/p&gt;&lt;p&gt;Barboza J.A., Liu G., El-Naggar A.K., Lozano G. p21 delays tumor onset by preservation of chromosomal stability. Proc Natl Acad Sci USA 2006;103:19842-7.&lt;/p&gt;&lt;p&gt;Janicke R.U., Sohn D., Schulze-Osthoff K. The dark side of a tumor suppressor: anti-apoptotic p53. Cell Death Differ 2008;15:959-76.&lt;/p&gt;&lt;p&gt;Liu B., Chen Y., St Clair D.K. ROS and p53: a verstile partnership. Free Radic Biol Med 2008;44:1529-35.&lt;/p&gt;&lt;p&gt;Sablina A.A., Budanov A.V., Ilyinskaya G.V. et al. The antioxidant function of the p53 tumor suppressor gene. Nat Med 2005;11:1306-13.&lt;/p&gt;&lt;p&gt;Bensaad K., Tsuruta A., Selak M.A. et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 2006;126:107-20.&lt;/p&gt;&lt;p&gt;Bensaad K., Vousden K.H. p53: new roles in metabolism. Trends Cell Biol 2007;17:286-91.&lt;/p&gt;&lt;p&gt;DeBerardinis R.J., Lum J.J., Hatzivassilou G., Thompson C.B. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 2008;7:11-20.&lt;/p&gt;&lt;p&gt;Bonnet S., Archer S.L., Allalunis-Turner J. et al. A mitochondrial-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer cell growth. Cancer Cell 2007;11:37-51.&lt;/p&gt;&lt;p&gt;Christofk H.R., Vander Heiden M.G., Harris M.H. et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumor growth. Nature 2008;452:230-3.&lt;/p&gt;&lt;p&gt;Fantin V.R., Syt-Pierre J., Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, micochondrial physiology, and tumor maintenance. Cancer Cell 2006;9:425-34.&lt;/p&gt;&lt;p&gt;Jones R.G., Plas D.R., Kubek S. et al. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 2005;18:283-93.&lt;/p&gt;&lt;p&gt;Budanov A.V., Karin M. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell 2008;134:451-60.&lt;/p&gt;&lt;p&gt;Feng Z., Hu W., de Stanchina E. et al. The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKTmTOR pathways. Cancer Res 2007;67:3043-53.&lt;/p&gt;&lt;p&gt;Crighton D., Wilkinson S., O'Prey J. et al. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell 2006;14:121-34.&lt;/p&gt;&lt;p&gt;Matthew R., Karantza-Wadsworth V., White E. Role of autophagy in cancer. Nat Rev Cancer 2007;7:961-7.&lt;/p&gt;&lt;p&gt;Tasdemir E., Maiuri M.C., Galluzzi L. et al. Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 2008;10:676-87.&lt;/p&gt;&lt;p&gt;Amaravadi R.K., Yu D., Lum J.J. et al. Autophagy inhibition enhances therapyinduced apoptosis in a Myc-induced model of lymphoma. J Clin Invest 2007;117:326-36.&lt;/p&gt;&lt;p&gt;Jones R.G., Thompson C.B. Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev 2009;23:537-48.&lt;/p&gt;&lt;p&gt;Kawauchi K., Araki K., Tobiume K., Tanaka N. p53 regulates glucose metabolism though an IKK-NF-kB pathway and inhibits cell transformation. Nat Cell Biol 2008;10:611-8.&lt;/p&gt;&lt;p&gt;Ma W., Sung H.J., Park J.Y. et al. A pivotal role for p53: balancing aerobic respiration and glycolysis. J Bioenerg Biomembr 2007;39:243-6.&lt;/p&gt;&lt;p&gt;Kondoh H., Lleonart M.E., Gil J. et al. Glycolytic enzymes can modulate cellular lifespan. Cancer Res 2005;65:177-85.&lt;/p&gt;&lt;p&gt;Christophorou M.A., Ringhausen I., Finch A.J. The pathological p53-mediated response to DNA damage is distinct from p53-mediated tumor suppression. Nature 2006;14:214-7.&lt;/p&gt;&lt;p&gt;Efeyan A., Garcia-Cao I., Herranz D. et al. Policing of oncogene activity by p53. Nature 2006;443:159.&lt;/p&gt;&lt;p&gt;Berns A. Cancer biology: can less be more for p53? Nature 2006;443:153-4.&lt;/p&gt;&lt;p&gt;Liu P., Xu B., Cavalieri T.A., Hock C.E. Pifithrin-alpha attenuates p53-mediated apoptosis and improves cardiac function in response to myocardialischemia/reperfusion in aged rats. Shock 2006;26:608-14.&lt;/p&gt;&lt;p&gt;Montanaro L., Trere D., Derenzini M. Nucleolus, ribosomes, and cancer. Am J Pathol 2008;173:301-10.&lt;/p&gt;&lt;p&gt;Jones N.C., Lynn M.L., Gaudenz K. et al. Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nat Med 2008;14:125-33.&lt;/p&gt;&lt;p&gt;Bae B.I., Xu H., Igarashi S. et al. p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. Neuron 2005;47:29-41.&lt;/p&gt;&lt;p&gt;Bretaud S., Allen C., Ingham P.W., Bandmann O. p53-dependent neuronal cell death in a DJ-1-deficient zebrafish model of Parkinson's disease. J Neurochem 2007;100:1626-35.&lt;/p&gt;&lt;p&gt;Culmsee C., Landshamer S. Molecular insights into mechanisms of the cell death program: role in the progression of neurodegenerative disorders. Curr Alzheimer Res 2006;3:269-83.&lt;/p&gt;&lt;p&gt;Lanni C., Uberti D., Racchi M. et al. Unfolded p53: a potential biomarker for Alzheimer's disease. J Alzheimers Dis 2007;12:93-9&lt;/p&gt;&lt;p&gt;Di Giovanni S., Knights C.D., Rao M. et al. The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration. EMBO J 2006;25:4084-96.&lt;/p&gt;&lt;p&gt;Aranda-Anzaldo A., Dent M.A. Reassessing the role of p53 in cancer and ageing from an evolutionary perspective. Mech Ageing Dev 2007;128:293-302.&lt;/p&gt;&lt;p&gt;Vousden K.H., Lane D.P. p53 in health and disease. Nat Rev Mol Cell Biol 2007;8:275-83.&lt;/p&gt;&lt;p&gt;Derry W.B., Putzke A.P., Rothman J.H. Caenorhabditis elegans p53: role in apoptosis, meiosis and stress resistance. Science 2001;294:591-5.&lt;/p&gt;&lt;p&gt;Sutcliffe J.E., Brehm A. Of flies and men; p53, a tumour suppressor. FEBS Lett 2004;567:86-91.&lt;/p&gt;&lt;p&gt;Piccolo S. p53 regulation orchestrates the TGF-beta response. Cell 2008;133:767-9.&lt;/p&gt;&lt;p&gt;Meletis K., Wirta V., Hede S.M. p53 suppresses the self-renewal of adult neural stem cells. Development 2006;133:363-9.&lt;/p&gt;&lt;p&gt;Liu Y., Elf S.E., Miyata Y. et al. p53 regulates hematopoietic stem cell quiescence. Cell Stem Cell 2009;4:37-48.&lt;/p&gt;&lt;p&gt;Godar S., Ince T.A., Bell G.W. et al. Growth-inhibitory and tumor-suppressive functions of p53 depend on its repression of CD44 expression. Cell 2008;134:62-73.&lt;/p&gt;&lt;p&gt;Hu W., Feng Z., Teresky A.K., Levine A.J. p53 regulates maternal reproduction through LIF. Nature 2007;450:721-4.&lt;/p&gt;&lt;p&gt;Kay C., Jeyendran R.S., Coulam C.B. p53 tumour suppressor gene polymorphism is associated with recurrent implantation failure. Reprod Biomed Online 2006;13:492-6.&lt;/p&gt;&lt;p&gt;Matoba S., Kang J.G., Patino W D. et al. p53 regulates mitochondrial respiration. Science 2006;312:1650-3.&lt;/p&gt;&lt;p&gt;Arum O., Johnson T.E. Reduced expression of the Caenorhabditis elegans p53 ortholog cep-1 results in increased longevity. J Gerontol Biol Sci Med Sci 2007;62:951-9.&lt;/p&gt;&lt;p&gt;Bauer J.H., Poon P.C., Glatt-Deeley H. et al. Neuronal expression of p53 dominant negative proteins in adult Drosophila melanogaster extends life span. Curr Biol 2005;15:2063-8.&lt;/p&gt;&lt;p&gt;Matheu A., Maraver A., Klatt P. et al. Delayed ageing through damage protection by the Arf/p53 pathway. Nature 2007;448:375-9.&lt;/p&gt;&lt;p&gt;Feng Z., Hu W., Teresky A.K. et al. Declining p53 function in the aging process: a possible mechanism for the increased tumor incidence in older populations. Proc Natl Acad Sci USA 2007;104:16633-8.&lt;/p&gt;&lt;p&gt;Moll U.M., Wolff S., Speidel D., Deppert W. Transcription-independent proapoptotic functions of p53. Curr Opin Cell Biol 2005;17:631-6.&lt;/p&gt;&lt;p&gt;Schuler M., Green D.R. Transcription, apoptosis and p53: catch-22. Trends Genet 2005;21:182-7.&lt;/p&gt;&lt;p&gt;Chipuk J.E., Bouchier-Hayes L., Kuwana T. et al. PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 2005;309:1732-5.&lt;/p&gt;&lt;p&gt;Riley T., Sontag E., Chen P., Levine A. Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol 2008;9:402-12.&lt;/p&gt;&lt;p&gt;Hoh J., Jin S., Parrado T. et al. The p53MH algorithm and its application in detecting p53-responsive genes. Proc Natl Acad Sci USA 2002;99:8467-72.&lt;/p&gt;&lt;p&gt;Miled C., Pontoglio M., Garbay S. et al. A genomic map of p53 binding sites identifies novel p53 targets involved in an apoptotic network. Cancer Res 2005;65:5096-104.&lt;/p&gt;&lt;p&gt;Sbisa E., Catalano D., Grillo G. et al. p53FamTaG: a database resource of human p53, p63 and p73 direct target genes combining in silico prediction and microarray data. BMC Bioinformatics 2007;8(Suppl. 1):S20.&lt;/p&gt;&lt;p&gt;Cawley S., Bekiranov S., Ng H.H. et al. Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 2004;116:499-509.&lt;/p&gt;&lt;p&gt;Hearnes J.M., Mays D.J., Schavolt K.L. et al. Chromatin immunoprecipitationbased screen to identify functional genomic binding sites for sequence-specific transactivators. Mol Cell Biol 2005;25:10148-58.&lt;/p&gt;&lt;p&gt;Smeenk L., van Heeringen S.J., Koeppel M. et al. Characterization of genome-wide p53-binding sites upon stress response. Nucleic Acids Res 2008;36:3639-54.&lt;/p&gt;&lt;p&gt;Jordan J.J., Menendez D., Inga A. et al. Noncanonical DNA motifs as transactivation targets by wild type and mutant p53. PLoS Genet 2008;4:e1000104.&lt;/p&gt;&lt;p&gt;Imbriano C., Gurtner A., Cocchiarella F. et al. Direct p53 transcriptional repression: in vivo analysis of CCAAT-containing G2/M promoters. Mol Cell Biol 2005;25:3737-51.&lt;/p&gt;&lt;p&gt;Laptenko O., Prives C. Transcriptional regulation by p53: one protein, many possibilities. Cell Death Differ 2006;13:951-96.&lt;/p&gt;&lt;p&gt;Lohr K., Moritz C., Contente A., Dobbelstein M. p21/CDKN1A mediates negative regulation of transcription by p53. J Biol Chem 2003;278:32507-16.&lt;/p&gt;&lt;p&gt;Shats I., Milyavsky M., Tang X. et al. p53-dependent down-regulation of telomerase is mediated by p21waf1. J Biol Chem 2004;279:50976-85.&lt;/p&gt;&lt;p&gt;Tang X., Milyavsky M., Shats I. et al. Activated p53 suppresses the histone methyltransferase EZH2 gene. Oncogene 2004;23:5759-69.&lt;/p&gt;&lt;p&gt;Esteve P.O., Chin H.G., Pradhan S. Molecular mechanisms of transactivation and doxorubicin-mediated repression of survivin gene in cancer cells. J Biol Chem 2007;282:2615-25.&lt;/p&gt;&lt;p&gt;Zaky A., Busso C., Izumi T. et al. Regulation of the human AP-endonuclease (APE1/Ref-1) expression by the tumor suppressor p53 in response to DNA damage. Nucleic Acids Res 2008;36:1555-66.&lt;/p&gt;&lt;p&gt;Matsui T., Katsuno Y., Inoue T. et al. Negative regulation of Chk2 expression by p53 is dependent on the CCAAT-binding transcription factor NF-Y. J Biol Chem 2004;279:25093-100.&lt;/p&gt;&lt;p&gt;Wilkinson D.S., Tsai W.W., Schumacher M.A., Barton M.C. Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growthfactor- beta-mediated transcription repression. Mol Cell Biol 2008;28:1988-98.&lt;/p&gt;&lt;p&gt;Johnson R.A., Ince T.A., Scotto K.W. Transcriptional repression by p53 through direct binding to a novel DNA element. J Biol Chem 2001;276:27716-20.&lt;/p&gt;&lt;p&gt;McKinney K., Mattia M., Gottifredi V., Prives C. p53 linear diffusion along DNA requires its C terminus. Mol Cell 2004;16:413-24.&lt;/p&gt;&lt;p&gt;Tafvizi A., Huang F., Leith J.S. et al. Tumor suppressor p53 slides on DNA with low friction and high stability. Biophys J 2008;95:L01-L03.&lt;/p&gt;&lt;p&gt;Augustyn K.E., Merino E.J., Barton J.K. A role for DNA-mediated charge transport in regulating p53: Oxidation of the DNA-bound protein from a distance. Proc Natl Acad Sci USA 2007;104:18907-12.&lt;/p&gt;&lt;p&gt;Bourdon J.C., Fernandes K., Murray-Zmijewski F. et al. p53 isoforms can regulate p53 transcriptional activity. Genes Dev 2005;19:2122-37.&lt;/p&gt;&lt;p&gt;Wei G., Li A.G., Liu X. Insights into selective activation of p53 DNA binding by c-Abl. J Biol Chem 2005;280:12271-8.&lt;/p&gt;&lt;p&gt;Sullivan A., Lu X. ASPP: a new family of oncogenes and tumour suppressor genes. Br J Cancer 2007;96:196-200.&lt;/p&gt;&lt;p&gt;Das S., Raj L., Zhao B. et al. Determines cell survival upon genotoxic stress by modulating p53 transactivation. Cell 2007;130:624-37.&lt;/p&gt;&lt;p&gt;McLure K.G., Takagi M., Kastan M.B. NAD+ modulates p53 DNA binding specificity and function. Mol Cell Biol 2004;24:9958-67.&lt;/p&gt;&lt;/div&gt;&lt;br /&gt;</mixed-citation><mixed-citation xml:lang="en">&lt;div&gt;&lt;p&gt;Firestein G.S., Echeverri F., Yeo M. et al. Somatic mutations in the p53 tumor suppressor gene in rheumatoid arthritis synovium. Proc Natl Acad Sci USA 1997;94:10895-900.&lt;/p&gt;&lt;p&gt;Yamanishi Y., Boyle D.L., Rosengren S. et al. Regional analysis of p53 mutations in rheumatoid arthritis synovium. Proc Natl Acad Sci USA 2002;99:10025-30.&lt;/p&gt;&lt;p&gt;Pap T., Aupperle K.R., Gay S. Invasiveness of synovial fibroblasts is regulated by p53 in the SCID mouse in vivo model of cartilage invasion. Arthr Rheum 2001;44:676-81.&lt;/p&gt;&lt;p&gt;Yao Q., Wang S., Glorioso J.C. et al. Gene transfer of p53 to arthritic joints stimulates synovial apoptosis and inhibits inflammation. Mol Theor 2001;3:901-10.&lt;/p&gt;&lt;p&gt;Yamanishi Y., Boyle D.L., Pinkoski M.J. et al. Regulation of joint destruction and inflammation by p53 in collagen-induced arthritis. Am J Pathol 2002;160:123-30.&lt;/p&gt;&lt;p&gt;Leech M., Xue J.R., Dacumos A. et al. The tumour suppressor gene p53 modulates the severity of antigen-induced arthritis and the systemic immune response. Clin Exp Immunol 2008;152(2):345-53.&lt;/p&gt;&lt;p&gt;Yu J., Zhang L. No PUMA, no death: implications for p53-dependent apoptosis. Cancer Cell 2003;4:248-9.&lt;/p&gt;&lt;p&gt;Michalak E.M., Villunger A., Adams J.M., Strasser A. In several cell types tumour suppressor p53 induces apoptosis largely via Puma but Noxa can contribute. Cell Death Differ 2008;15:1019-29.&lt;/p&gt;&lt;p&gt;Garrison S.P., Jeffers J.R., Yang C. et al. Selection against PUMA gene expression in Myc-driven B cell lymphomagenesis. Mol Cell Biol 2008;28:5391-402.&lt;/p&gt;&lt;p&gt;Hemann M.T., Zilfou J.T., Zhao Z. et al. Suppression of tumorigenesis by the p53 target PUMA. Proc Natl Acad Sci USA 2004;101:9333-8.&lt;/p&gt;&lt;p&gt;Rowan S., Ludwig R.L., Haupt Y. et al. Specific loss of apoptotic but not cell cycle arrest function in a human tumour derived p53 mutant. EMBO J 1996;15:827-38.&lt;/p&gt;&lt;p&gt;Liu G., Parant J.M., Lang G. et al. Chromosomal stability, in the absence of apoptosis, is critical for suppression of tumorigenesis in Trp53 mutant mice. Nat Genet 2004;36:63-8.&lt;/p&gt;&lt;p&gt;El-Deiry W.S. Regulation of p53 downstream genes. Semin. Cancer Biol 1998;8:345-57.&lt;/p&gt;&lt;p&gt;Deng Y., Chan S.S., Chang S. Telomere dysfunction and tumour suppression: the senescence connection. Nat Rev Cancer 2008;8:450-8.&lt;/p&gt;&lt;p&gt;Halazonetis T.D., Gorgoulis V.G.,Barteck J. An oncogene-induced DNA damage model for cancer development. Science 2008;319:1352-5.&lt;/p&gt;&lt;p&gt;Martins C.P., Brown-Swigart L., Evan G.I. Modeling the therapeutic efficacy of p53 restoration in tumors. Cell 2006;127:1323-34.&lt;/p&gt;&lt;p&gt;Ventura A., Kirsch D.G., McLaughlin M.E. et al. Restoration of p53 function leads to tumour regression in vivo. Nature 2007;445:661-5.&lt;/p&gt;&lt;p&gt;Xue W., Zender L., Miething C. et al. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 2007;445:656-60.&lt;/p&gt;&lt;p&gt;Brown J.P., Wei W., Sedivy J.M. Bypass of senescence after disruption of p21CIP1/WAF1 gene in normal diploid human fibroblasts. Science 1997;277:831-4.&lt;/p&gt;&lt;p&gt;Cosme-Blanco W., Shen M.-F., Lazar A.J.F. et al. Telomere dysfunction suppresses spontaneous tumorigeesis in vivo by initiating p53-dependent cellular senescence. EMBO Rep 2007;8:497-503&lt;/p&gt;&lt;p&gt;Van Nguyen T., Puebla-Osorio N., Pang H. et al. DNA damage-induced cellular senescence is sufficient to suppress tumorigenesis: a mouse model. J Exp Med 2007;204:1453-61.&lt;/p&gt;&lt;p&gt;Barboza J.A., Liu G., El-Naggar A.K., Lozano G. p21 delays tumor onset by preservation of chromosomal stability. Proc Natl Acad Sci USA 2006;103:19842-7.&lt;/p&gt;&lt;p&gt;Janicke R.U., Sohn D., Schulze-Osthoff K. The dark side of a tumor suppressor: anti-apoptotic p53. Cell Death Differ 2008;15:959-76.&lt;/p&gt;&lt;p&gt;Liu B., Chen Y., St Clair D.K. ROS and p53: a verstile partnership. Free Radic Biol Med 2008;44:1529-35.&lt;/p&gt;&lt;p&gt;Sablina A.A., Budanov A.V., Ilyinskaya G.V. et al. The antioxidant function of the p53 tumor suppressor gene. Nat Med 2005;11:1306-13.&lt;/p&gt;&lt;p&gt;Bensaad K., Tsuruta A., Selak M.A. et al. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 2006;126:107-20.&lt;/p&gt;&lt;p&gt;Bensaad K., Vousden K.H. p53: new roles in metabolism. Trends Cell Biol 2007;17:286-91.&lt;/p&gt;&lt;p&gt;DeBerardinis R.J., Lum J.J., Hatzivassilou G., Thompson C.B. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 2008;7:11-20.&lt;/p&gt;&lt;p&gt;Bonnet S., Archer S.L., Allalunis-Turner J. et al. A mitochondrial-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer cell growth. Cancer Cell 2007;11:37-51.&lt;/p&gt;&lt;p&gt;Christofk H.R., Vander Heiden M.G., Harris M.H. et al. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumor growth. Nature 2008;452:230-3.&lt;/p&gt;&lt;p&gt;Fantin V.R., Syt-Pierre J., Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, micochondrial physiology, and tumor maintenance. Cancer Cell 2006;9:425-34.&lt;/p&gt;&lt;p&gt;Jones R.G., Plas D.R., Kubek S. et al. AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol Cell 2005;18:283-93.&lt;/p&gt;&lt;p&gt;Budanov A.V., Karin M. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell 2008;134:451-60.&lt;/p&gt;&lt;p&gt;Feng Z., Hu W., de Stanchina E. et al. The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKTmTOR pathways. Cancer Res 2007;67:3043-53.&lt;/p&gt;&lt;p&gt;Crighton D., Wilkinson S., O'Prey J. et al. DRAM, a p53-induced modulator of autophagy, is critical for apoptosis. Cell 2006;14:121-34.&lt;/p&gt;&lt;p&gt;Matthew R., Karantza-Wadsworth V., White E. Role of autophagy in cancer. Nat Rev Cancer 2007;7:961-7.&lt;/p&gt;&lt;p&gt;Tasdemir E., Maiuri M.C., Galluzzi L. et al. Regulation of autophagy by cytoplasmic p53. Nat Cell Biol 2008;10:676-87.&lt;/p&gt;&lt;p&gt;Amaravadi R.K., Yu D., Lum J.J. et al. Autophagy inhibition enhances therapyinduced apoptosis in a Myc-induced model of lymphoma. J Clin Invest 2007;117:326-36.&lt;/p&gt;&lt;p&gt;Jones R.G., Thompson C.B. Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev 2009;23:537-48.&lt;/p&gt;&lt;p&gt;Kawauchi K., Araki K., Tobiume K., Tanaka N. p53 regulates glucose metabolism though an IKK-NF-kB pathway and inhibits cell transformation. Nat Cell Biol 2008;10:611-8.&lt;/p&gt;&lt;p&gt;Ma W., Sung H.J., Park J.Y. et al. A pivotal role for p53: balancing aerobic respiration and glycolysis. J Bioenerg Biomembr 2007;39:243-6.&lt;/p&gt;&lt;p&gt;Kondoh H., Lleonart M.E., Gil J. et al. Glycolytic enzymes can modulate cellular lifespan. Cancer Res 2005;65:177-85.&lt;/p&gt;&lt;p&gt;Christophorou M.A., Ringhausen I., Finch A.J. The pathological p53-mediated response to DNA damage is distinct from p53-mediated tumor suppression. Nature 2006;14:214-7.&lt;/p&gt;&lt;p&gt;Efeyan A., Garcia-Cao I., Herranz D. et al. Policing of oncogene activity by p53. Nature 2006;443:159.&lt;/p&gt;&lt;p&gt;Berns A. Cancer biology: can less be more for p53? Nature 2006;443:153-4.&lt;/p&gt;&lt;p&gt;Liu P., Xu B., Cavalieri T.A., Hock C.E. Pifithrin-alpha attenuates p53-mediated apoptosis and improves cardiac function in response to myocardialischemia/reperfusion in aged rats. Shock 2006;26:608-14.&lt;/p&gt;&lt;p&gt;Montanaro L., Trere D., Derenzini M. Nucleolus, ribosomes, and cancer. Am J Pathol 2008;173:301-10.&lt;/p&gt;&lt;p&gt;Jones N.C., Lynn M.L., Gaudenz K. et al. Prevention of the neurocristopathy Treacher Collins syndrome through inhibition of p53 function. Nat Med 2008;14:125-33.&lt;/p&gt;&lt;p&gt;Bae B.I., Xu H., Igarashi S. et al. p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease. Neuron 2005;47:29-41.&lt;/p&gt;&lt;p&gt;Bretaud S., Allen C., Ingham P.W., Bandmann O. p53-dependent neuronal cell death in a DJ-1-deficient zebrafish model of Parkinson's disease. J Neurochem 2007;100:1626-35.&lt;/p&gt;&lt;p&gt;Culmsee C., Landshamer S. Molecular insights into mechanisms of the cell death program: role in the progression of neurodegenerative disorders. Curr Alzheimer Res 2006;3:269-83.&lt;/p&gt;&lt;p&gt;Lanni C., Uberti D., Racchi M. et al. Unfolded p53: a potential biomarker for Alzheimer's disease. J Alzheimers Dis 2007;12:93-9&lt;/p&gt;&lt;p&gt;Di Giovanni S., Knights C.D., Rao M. et al. The tumor suppressor protein p53 is required for neurite outgrowth and axon regeneration. EMBO J 2006;25:4084-96.&lt;/p&gt;&lt;p&gt;Aranda-Anzaldo A., Dent M.A. Reassessing the role of p53 in cancer and ageing from an evolutionary perspective. Mech Ageing Dev 2007;128:293-302.&lt;/p&gt;&lt;p&gt;Vousden K.H., Lane D.P. p53 in health and disease. Nat Rev Mol Cell Biol 2007;8:275-83.&lt;/p&gt;&lt;p&gt;Derry W.B., Putzke A.P., Rothman J.H. Caenorhabditis elegans p53: role in apoptosis, meiosis and stress resistance. Science 2001;294:591-5.&lt;/p&gt;&lt;p&gt;Sutcliffe J.E., Brehm A. Of flies and men; p53, a tumour suppressor. FEBS Lett 2004;567:86-91.&lt;/p&gt;&lt;p&gt;Piccolo S. p53 regulation orchestrates the TGF-beta response. Cell 2008;133:767-9.&lt;/p&gt;&lt;p&gt;Meletis K., Wirta V., Hede S.M. p53 suppresses the self-renewal of adult neural stem cells. Development 2006;133:363-9.&lt;/p&gt;&lt;p&gt;Liu Y., Elf S.E., Miyata Y. et al. p53 regulates hematopoietic stem cell quiescence. Cell Stem Cell 2009;4:37-48.&lt;/p&gt;&lt;p&gt;Godar S., Ince T.A., Bell G.W. et al. Growth-inhibitory and tumor-suppressive functions of p53 depend on its repression of CD44 expression. Cell 2008;134:62-73.&lt;/p&gt;&lt;p&gt;Hu W., Feng Z., Teresky A.K., Levine A.J. p53 regulates maternal reproduction through LIF. Nature 2007;450:721-4.&lt;/p&gt;&lt;p&gt;Kay C., Jeyendran R.S., Coulam C.B. p53 tumour suppressor gene polymorphism is associated with recurrent implantation failure. Reprod Biomed Online 2006;13:492-6.&lt;/p&gt;&lt;p&gt;Matoba S., Kang J.G., Patino W D. et al. p53 regulates mitochondrial respiration. Science 2006;312:1650-3.&lt;/p&gt;&lt;p&gt;Arum O., Johnson T.E. Reduced expression of the Caenorhabditis elegans p53 ortholog cep-1 results in increased longevity. J Gerontol Biol Sci Med Sci 2007;62:951-9.&lt;/p&gt;&lt;p&gt;Bauer J.H., Poon P.C., Glatt-Deeley H. et al. Neuronal expression of p53 dominant negative proteins in adult Drosophila melanogaster extends life span. Curr Biol 2005;15:2063-8.&lt;/p&gt;&lt;p&gt;Matheu A., Maraver A., Klatt P. et al. Delayed ageing through damage protection by the Arf/p53 pathway. Nature 2007;448:375-9.&lt;/p&gt;&lt;p&gt;Feng Z., Hu W., Teresky A.K. et al. Declining p53 function in the aging process: a possible mechanism for the increased tumor incidence in older populations. Proc Natl Acad Sci USA 2007;104:16633-8.&lt;/p&gt;&lt;p&gt;Moll U.M., Wolff S., Speidel D., Deppert W. Transcription-independent proapoptotic functions of p53. Curr Opin Cell Biol 2005;17:631-6.&lt;/p&gt;&lt;p&gt;Schuler M., Green D.R. Transcription, apoptosis and p53: catch-22. Trends Genet 2005;21:182-7.&lt;/p&gt;&lt;p&gt;Chipuk J.E., Bouchier-Hayes L., Kuwana T. et al. PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 2005;309:1732-5.&lt;/p&gt;&lt;p&gt;Riley T., Sontag E., Chen P., Levine A. Transcriptional control of human p53-regulated genes. Nat Rev Mol Cell Biol 2008;9:402-12.&lt;/p&gt;&lt;p&gt;Hoh J., Jin S., Parrado T. et al. The p53MH algorithm and its application in detecting p53-responsive genes. Proc Natl Acad Sci USA 2002;99:8467-72.&lt;/p&gt;&lt;p&gt;Miled C., Pontoglio M., Garbay S. et al. A genomic map of p53 binding sites identifies novel p53 targets involved in an apoptotic network. Cancer Res 2005;65:5096-104.&lt;/p&gt;&lt;p&gt;Sbisa E., Catalano D., Grillo G. et al. p53FamTaG: a database resource of human p53, p63 and p73 direct target genes combining in silico prediction and microarray data. BMC Bioinformatics 2007;8(Suppl. 1):S20.&lt;/p&gt;&lt;p&gt;Cawley S., Bekiranov S., Ng H.H. et al. Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs. Cell 2004;116:499-509.&lt;/p&gt;&lt;p&gt;Hearnes J.M., Mays D.J., Schavolt K.L. et al. Chromatin immunoprecipitationbased screen to identify functional genomic binding sites for sequence-specific transactivators. Mol Cell Biol 2005;25:10148-58.&lt;/p&gt;&lt;p&gt;Smeenk L., van Heeringen S.J., Koeppel M. et al. Characterization of genome-wide p53-binding sites upon stress response. Nucleic Acids Res 2008;36:3639-54.&lt;/p&gt;&lt;p&gt;Jordan J.J., Menendez D., Inga A. et al. Noncanonical DNA motifs as transactivation targets by wild type and mutant p53. PLoS Genet 2008;4:e1000104.&lt;/p&gt;&lt;p&gt;Imbriano C., Gurtner A., Cocchiarella F. et al. Direct p53 transcriptional repression: in vivo analysis of CCAAT-containing G2/M promoters. Mol Cell Biol 2005;25:3737-51.&lt;/p&gt;&lt;p&gt;Laptenko O., Prives C. Transcriptional regulation by p53: one protein, many possibilities. Cell Death Differ 2006;13:951-96.&lt;/p&gt;&lt;p&gt;Lohr K., Moritz C., Contente A., Dobbelstein M. p21/CDKN1A mediates negative regulation of transcription by p53. J Biol Chem 2003;278:32507-16.&lt;/p&gt;&lt;p&gt;Shats I., Milyavsky M., Tang X. et al. p53-dependent down-regulation of telomerase is mediated by p21waf1. J Biol Chem 2004;279:50976-85.&lt;/p&gt;&lt;p&gt;Tang X., Milyavsky M., Shats I. et al. Activated p53 suppresses the histone methyltransferase EZH2 gene. Oncogene 2004;23:5759-69.&lt;/p&gt;&lt;p&gt;Esteve P.O., Chin H.G., Pradhan S. Molecular mechanisms of transactivation and doxorubicin-mediated repression of survivin gene in cancer cells. J Biol Chem 2007;282:2615-25.&lt;/p&gt;&lt;p&gt;Zaky A., Busso C., Izumi T. et al. Regulation of the human AP-endonuclease (APE1/Ref-1) expression by the tumor suppressor p53 in response to DNA damage. Nucleic Acids Res 2008;36:1555-66.&lt;/p&gt;&lt;p&gt;Matsui T., Katsuno Y., Inoue T. et al. Negative regulation of Chk2 expression by p53 is dependent on the CCAAT-binding transcription factor NF-Y. J Biol Chem 2004;279:25093-100.&lt;/p&gt;&lt;p&gt;Wilkinson D.S., Tsai W.W., Schumacher M.A., Barton M.C. Chromatin-bound p53 anchors activated Smads and the mSin3A corepressor to confer transforming-growthfactor- beta-mediated transcription repression. Mol Cell Biol 2008;28:1988-98.&lt;/p&gt;&lt;p&gt;Johnson R.A., Ince T.A., Scotto K.W. Transcriptional repression by p53 through direct binding to a novel DNA element. J Biol Chem 2001;276:27716-20.&lt;/p&gt;&lt;p&gt;McKinney K., Mattia M., Gottifredi V., Prives C. p53 linear diffusion along DNA requires its C terminus. Mol Cell 2004;16:413-24.&lt;/p&gt;&lt;p&gt;Tafvizi A., Huang F., Leith J.S. et al. Tumor suppressor p53 slides on DNA with low friction and high stability. Biophys J 2008;95:L01-L03.&lt;/p&gt;&lt;p&gt;Augustyn K.E., Merino E.J., Barton J.K. A role for DNA-mediated charge transport in regulating p53: Oxidation of the DNA-bound protein from a distance. Proc Natl Acad Sci USA 2007;104:18907-12.&lt;/p&gt;&lt;p&gt;Bourdon J.C., Fernandes K., Murray-Zmijewski F. et al. p53 isoforms can regulate p53 transcriptional activity. Genes Dev 2005;19:2122-37.&lt;/p&gt;&lt;p&gt;Wei G., Li A.G., Liu X. Insights into selective activation of p53 DNA binding by c-Abl. J Biol Chem 2005;280:12271-8.&lt;/p&gt;&lt;p&gt;Sullivan A., Lu X. ASPP: a new family of oncogenes and tumour suppressor genes. Br J Cancer 2007;96:196-200.&lt;/p&gt;&lt;p&gt;Das S., Raj L., Zhao B. et al. Determines cell survival upon genotoxic stress by modulating p53 transactivation. Cell 2007;130:624-37.&lt;/p&gt;&lt;p&gt;McLure K.G., Takagi M., Kastan M.B. NAD+ modulates p53 DNA binding specificity and function. Mol Cell Biol 2004;24:9958-67.&lt;/p&gt;&lt;/div&gt;&lt;br /&gt;</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
