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Fecha Publicación: 2009-12-18
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Baena Valencia, J. C., Peláez Giraldo, I., & Castaño Molina, E. (2009). P53: La historia sin final de un polifacético guardián. Biosalud, 8, 217–230. Recuperado a partir de https://revistasojs.ucaldas.edu.co/index.php/biosalud/article/view/5541
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El gen p53 ha sido muy estudiado en los últimos años. Inicialmente su producto fue considerado como promotor tumoral; pero hoy en día no sólo se le reconocen sus bondades como un represor tumoral, sino que también juega un papel protagónico en otros procesos celulares como el mantenimiento de la integridad del genoma, la apoptosis, la senescencia y el desarrollo, entre otros. Pero, aún no se conoce los límites de sus alcances; sin embargo la información obtenida ha logrado transcender a las aplicaciones clínicas y probablemente falta mucho más por explorar y aplicar acerca de éste polifacético guardián.
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Knudson AG Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U.S.A. 1971;68:820-823.
Sell S, Pierce GB. Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. Lab Invest 1994;70:6-22.
Lane DP, Benchimol S. p53: oncogene or anti-oncogene? Genes Dev 1990;4:1-8.
Levine AJ, Finlay CA, Hinds PW. p53 is a Tumor Suppressor Gene. Cell. 2004;116(2 Suppl):S67-69.
Calabretta B, Kaczmarek L, Selleri L, Torelli G, Ming PM, Ming SC, Mercer WE. Growth-dependent Expression of Human Mr 53,000 Tumor Antigen MessengerRNA in Normal and Neoplastic Cells. Cancer Res 1986;46:5738-5742.
Chumakov PM. Versatile Functions of p53 Protein in Multicellular Organisms. Biochemistry (Mosc).2007;72:1399-1421.
DeLeo AB, Jay G, Appella E, Dubois GC, Law LW, Old LJ. Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Proc Natl Acad Sci U.S.A. 1979;76:2420-2424.
Dippold WG, Jay G, DeLeo AB, Khoury G, Old LJ. p53 transformation-related protein: Detection by monoclonal antibody in mouse and human cells. Proc Natl Acad Sci U.S.A. 1981;78(3):1695-1699.
Mercer WE, Avignolo C, Baserga R. Role of the p53 Protein in Cell Proliferation as Studied by Microinjection of Monoclonal Antibodies. Mol Cell Biol 1984;4:276-281.
Reich NC, Oren M, Levine AJ. Two Distinct Mechanisms Regulate the Levels of a Cellular Tumor Antigen, p53. Mol Cell Biol 1983; 3:2143-2150.
Oren M, Levine AJ. Molecular cloning of a cDNA specific for the murine p53 cellular tumor antigen. Proc Natl Acad Sci U.S.A. 1983; 80:56-59.
Oren M, Bienz B, Givol D, Rechavi G, Zakut R. Analysis of recombinant DNA clones specific for the murine p53 cellular tumor antigen. EMBO J 1983;2:1633-1639.
Pinhasi O, Oren M. Expression of the Mouse p53 Cellular Tumor Antigen in Monkey Cells. Mol Cell Biol 1984;4:2180-2186.
Leppard K, Totty N, Waterfield M, Harlow E, Jenkins J, Crawford L. Purification and partial amino acid sequence analysis of the cellular tumour antigen, p53, from mouse SV40-transformed cells. EMBO J 1983;2:1993-1999.
Harvey D M; Levine A J. p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts. Genes Dev 1991;5:2375-2385.
Hinds P, Finlay C, Levine AJ. Mutation Is Required To Activate the p53 Gene for Cooperation with the ras Oncogene and Transformation. J Virol 1989; 63:739-746.
Lavigueur A, Maltby V, Mock D, Rossant J, Pawson T, Bernstein A. High Incidence of Lung, Bone, and Lymphoid Tumors in Transgenic Mice Overexpressing Mutant Alleles of the p53 Oncogene. Mol Cell Biol 1989;9:3982-3991.
Rovinski B, Munroe D, Peacock J, Mowat M, Bernstein A, Benchimol S. Deletion of 5’-Coding Sequences of the Cellular p53 Gene in Mouse Erythroleukemia: a Novel Mechanism of Oncogene Regulation.Mol Cell Biol 1987;7:847-853.
Oren M, Maltzman W, Levine AJ. Post-Translational Regulation of the 54K Cellular Tumor Antigen in Normal and Transformed Cells. Mol Cell Biol 1981;1:101-110.
Funk WD, Pak DT, Karas RH, Wright WE, Shay JW. A Transcriptionally Active DNA-Binding Site for Human p53 Protein Complexes. Mol Cell Biol 1992;12:2866-2871.
Zauberman A, Barak Y, Ragimov N, Levy N, Oren M. Sequence-specific DNA binding by p53: identification of target sites and lack of binding to p53 MDM2 complexes. EMBO J 1993;12:2799-2808.
Shaulian E, Zauberman A, Milner J, Davies EA, Oren M. Tight DNA binding and oligomerization are dispensable for the ability of p53 to transactivate target genes and suppress transformation. EMBO J 1993;12:2789-2797.
Fakharzadeh SS, Trusko SP, George DL. Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J 1991;10:1565-1569.
Cahilly-Snyder L, Yang-Feng T, Francke U, George DL. Somat. Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line. Cell Mol Genet 1987;13:235-244.
Chen J, Wu X, Lin J, Levine AJ. MDM-2 Inhibits the G1 Arrest and Apoptosis Functions of the p53 Tumor Suppressor Protein. Mol Cell Biol 1996;16:2445-2452.
Wu HH, Dasgupta G. MDM2, master regulator of the p53 tumor suppressor protein. Gene 2000;242(1-2):15-29.
X Wu, J H Bayle, D Olson, et al. The p53-mdm-2 autoregulatory feedback loop. Genes Dev 1993;7:1126-1132.
Honda R, Tanaka H, Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 1997;420(1):25-27.
Unger T, Juven-Gershon T, Moallem E, Berger M, Vogt Sionov R, Lozano G, Oren M, Haupt Y. Critical role for Ser20 of human p53 in the negative regulation of p53 by Mdm2. EMBO J 1999;18(7):1805-1814.
Unger T, Vogt Sionov R, Moallem E, Yee L. C, Howley P, Oren M, Haupt Y. Mutations in serines 15 and 20 of human p53 impair its apoptotic activity. Oncogene 1999;18:3205-3212.
Lin J, Chen J, Elenbaas B, et al. Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes Dev 1994;8(10):1235-46.
D.P.Lane. p53, guardian of the genome. Nature 1992;358:15-16.
DE Koshland, Jr. Molecule of the year. Science 1993;262:1953.
P.M. Chumakov. Function of the p53 Gene: Choice between Life and Death. Biochemistry (Moscow) 2000;65:28-40.
Harper JW, Elledge SJ, Keyomarsi K, Dynlacht B, Tsai LH, Zhang P, Dobrowolski S, Bai C, Connell-Crowley L, Swindell E, et al. Inhibition of Cyclin-dependent Kinases by p21. Mol Biol Cell 1995;6:387-400.
Su L, Sai Y, Fan R, Thurston SW, Miller DP, Zhou W, Wain JC, Lynch TJ, Liu G, Christiani DC. P53 (codon 72) and P21 (codon 31) polymorphisms alter in vivo mRNA expression of p21. Lung Cancer 2003;40:259-266.
Draetta G, Eckstein J. Cdc25 protein phosphatases in cell proliferation. Biochim Biophys Acta 1997;1332:53-63.
William Taylor WR, Stark GR. Regulation of the G2/M transition by p53. Oncogene 2001;5:1803-1815.
Hwang BJ, Ford JM, Hanawalt PC, Chu G. Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair. Proc Natl Acad Sci USA 1999;96:424-428.
Helton ES, Chen X. p53 modulation of the DNA damage response. J Cell Biochem 2007;100:883-896.
Thierry Rossé T, Olivier R, Monney L, Rager M, Conus S, Fellay I, Jansen B, Borner C. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Nature 1998;391:496-499.
Sheikh MS, Burns TF, Huang Y, Wu GS, Amundson S, Brooks KS, Fornace AJ Jr, el-Deiry WS. p53 dependent and -independent Regulation of the Death Receptor KILLER/DR5 Gene Expression in Response to Genotoxic Stress and Tumor Necrosis Factor alpha. Cancer Res 1998;58:1593-1598.
Nishimori H, Shiratsuchi T, Urano T, Kimura Y, Kiyono K, Tatsumi K, Yoshida S, Ono M, Kuwano M, Nakamura Y, Tokino T. A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis. Oncogene 1997;18:2145-2150.
Van Meir EG, Polverini PJ, Chazin VR, Su Huang HJ, de Tribolet N, Cavenee WK. Release of an inhibitor of angiogenesis upon induction of wild type p53 expression in glioblastoma cells. Nat Genet 1994;8:171-176.
Harada H, Nakagawa K, Saito M, Kohno S, Nagato S, Furukawa K, Kumon Y, Hamada K, Ohnishi T. Introduction of wild-type p53 enhances thrombospondin-1 expression in human glioma cells. Cancer Lett 2003;191:109-1019.
Hussain SP, Amstad P, He P, Robles A, Lupold S, Kaneko I, Ichimiya M, Sengupta S, Mechanic L, Okamura S, Hofseth LJ, Moake M, Nagashima M, Forrester KS, Harris CC. p53-induced up-regulation of MnSOD and GPx but not catalase increases oxidative stress and apoptosis. Cancer Res 2004;64:2350-2356.
Yoon KA, Nakamura Y, Arakawa H. Identification of ALDH4 as a p53-inducible gene and its protective role in cellular stresses. J Hum Genet 2004;49:134-1340.
Budanov AV, Sablina AA, Feinstein E, Koonin EV, Chumakov PM. Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science 2004;304:596-600.
Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E, Vousden KH. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 2006;126:107-120.
Bensaad K, Vousden KH. p53: new roles in metabolism. Trends Cell Biol 2007;17:286-291.
Lu X. p53: a heavily dictated dictator of life and death. Curr Opin Genet Dev 2005;15:27-33.
Erster S, Mihara M, Kim RH, Petrenko O, Moll UM. In vivo mitochondrial p53 translocation triggers a rapid first wave of cell death in response to DNA damage that can precede p53 target gene activation. Mol Cell Biol 2004;24:6728-41.
Murphy ME, Leu JI, George DL. p53 moves to mitochondria: a turn on the path to apoptosis. Cell Cycle 2004;3(7):836-9.
A.V. Vaseva, U.M. Moll. The mitochondrial p53 pathway. Biochimica et Biophysica Acta 2009;1787:414-420.
Taylor WR, DePrimo SE, Agarwal A, Agarwal ML, Schönthal AH, Katula KS, Stark GR. Mechanisms of G2 arrest in response to overexpression of p53.Mol Biol Cell 1999; 10:3607-36022.
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Knudson AG Jr. Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U.S.A. 1971;68:820-823.
Sell S, Pierce GB. Maturation arrest of stem cell differentiation is a common pathway for the cellular origin of teratocarcinomas and epithelial cancers. Lab Invest 1994;70:6-22.
Lane DP, Benchimol S. p53: oncogene or anti-oncogene? Genes Dev 1990;4:1-8.
Levine AJ, Finlay CA, Hinds PW. p53 is a Tumor Suppressor Gene. Cell. 2004;116(2 Suppl):S67-69.
Calabretta B, Kaczmarek L, Selleri L, Torelli G, Ming PM, Ming SC, Mercer WE. Growth-dependent Expression of Human Mr 53,000 Tumor Antigen MessengerRNA in Normal and Neoplastic Cells. Cancer Res 1986;46:5738-5742.
Chumakov PM. Versatile Functions of p53 Protein in Multicellular Organisms. Biochemistry (Mosc).2007;72:1399-1421.
DeLeo AB, Jay G, Appella E, Dubois GC, Law LW, Old LJ. Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Proc Natl Acad Sci U.S.A. 1979;76:2420-2424.
Dippold WG, Jay G, DeLeo AB, Khoury G, Old LJ. p53 transformation-related protein: Detection by monoclonal antibody in mouse and human cells. Proc Natl Acad Sci U.S.A. 1981;78(3):1695-1699.
Mercer WE, Avignolo C, Baserga R. Role of the p53 Protein in Cell Proliferation as Studied by Microinjection of Monoclonal Antibodies. Mol Cell Biol 1984;4:276-281.
Reich NC, Oren M, Levine AJ. Two Distinct Mechanisms Regulate the Levels of a Cellular Tumor Antigen, p53. Mol Cell Biol 1983; 3:2143-2150.
Oren M, Levine AJ. Molecular cloning of a cDNA specific for the murine p53 cellular tumor antigen. Proc Natl Acad Sci U.S.A. 1983; 80:56-59.
Oren M, Bienz B, Givol D, Rechavi G, Zakut R. Analysis of recombinant DNA clones specific for the murine p53 cellular tumor antigen. EMBO J 1983;2:1633-1639.
Pinhasi O, Oren M. Expression of the Mouse p53 Cellular Tumor Antigen in Monkey Cells. Mol Cell Biol 1984;4:2180-2186.
Leppard K, Totty N, Waterfield M, Harlow E, Jenkins J, Crawford L. Purification and partial amino acid sequence analysis of the cellular tumour antigen, p53, from mouse SV40-transformed cells. EMBO J 1983;2:1993-1999.
Harvey D M; Levine A J. p53 alteration is a common event in the spontaneous immortalization of primary BALB/c murine embryo fibroblasts. Genes Dev 1991;5:2375-2385.
Hinds P, Finlay C, Levine AJ. Mutation Is Required To Activate the p53 Gene for Cooperation with the ras Oncogene and Transformation. J Virol 1989; 63:739-746.
Lavigueur A, Maltby V, Mock D, Rossant J, Pawson T, Bernstein A. High Incidence of Lung, Bone, and Lymphoid Tumors in Transgenic Mice Overexpressing Mutant Alleles of the p53 Oncogene. Mol Cell Biol 1989;9:3982-3991.
Rovinski B, Munroe D, Peacock J, Mowat M, Bernstein A, Benchimol S. Deletion of 5’-Coding Sequences of the Cellular p53 Gene in Mouse Erythroleukemia: a Novel Mechanism of Oncogene Regulation.Mol Cell Biol 1987;7:847-853.
Oren M, Maltzman W, Levine AJ. Post-Translational Regulation of the 54K Cellular Tumor Antigen in Normal and Transformed Cells. Mol Cell Biol 1981;1:101-110.
Funk WD, Pak DT, Karas RH, Wright WE, Shay JW. A Transcriptionally Active DNA-Binding Site for Human p53 Protein Complexes. Mol Cell Biol 1992;12:2866-2871.
Zauberman A, Barak Y, Ragimov N, Levy N, Oren M. Sequence-specific DNA binding by p53: identification of target sites and lack of binding to p53 MDM2 complexes. EMBO J 1993;12:2799-2808.
Shaulian E, Zauberman A, Milner J, Davies EA, Oren M. Tight DNA binding and oligomerization are dispensable for the ability of p53 to transactivate target genes and suppress transformation. EMBO J 1993;12:2789-2797.
Fakharzadeh SS, Trusko SP, George DL. Tumorigenic potential associated with enhanced expression of a gene that is amplified in a mouse tumor cell line. EMBO J 1991;10:1565-1569.
Cahilly-Snyder L, Yang-Feng T, Francke U, George DL. Somat. Molecular analysis and chromosomal mapping of amplified genes isolated from a transformed mouse 3T3 cell line. Cell Mol Genet 1987;13:235-244.
Chen J, Wu X, Lin J, Levine AJ. MDM-2 Inhibits the G1 Arrest and Apoptosis Functions of the p53 Tumor Suppressor Protein. Mol Cell Biol 1996;16:2445-2452.
Wu HH, Dasgupta G. MDM2, master regulator of the p53 tumor suppressor protein. Gene 2000;242(1-2):15-29.
X Wu, J H Bayle, D Olson, et al. The p53-mdm-2 autoregulatory feedback loop. Genes Dev 1993;7:1126-1132.
Honda R, Tanaka H, Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 1997;420(1):25-27.
Unger T, Juven-Gershon T, Moallem E, Berger M, Vogt Sionov R, Lozano G, Oren M, Haupt Y. Critical role for Ser20 of human p53 in the negative regulation of p53 by Mdm2. EMBO J 1999;18(7):1805-1814.
Unger T, Vogt Sionov R, Moallem E, Yee L. C, Howley P, Oren M, Haupt Y. Mutations in serines 15 and 20 of human p53 impair its apoptotic activity. Oncogene 1999;18:3205-3212.
Lin J, Chen J, Elenbaas B, et al. Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes Dev 1994;8(10):1235-46.
D.P.Lane. p53, guardian of the genome. Nature 1992;358:15-16.
DE Koshland, Jr. Molecule of the year. Science 1993;262:1953.
P.M. Chumakov. Function of the p53 Gene: Choice between Life and Death. Biochemistry (Moscow) 2000;65:28-40.
Harper JW, Elledge SJ, Keyomarsi K, Dynlacht B, Tsai LH, Zhang P, Dobrowolski S, Bai C, Connell-Crowley L, Swindell E, et al. Inhibition of Cyclin-dependent Kinases by p21. Mol Biol Cell 1995;6:387-400.
Su L, Sai Y, Fan R, Thurston SW, Miller DP, Zhou W, Wain JC, Lynch TJ, Liu G, Christiani DC. P53 (codon 72) and P21 (codon 31) polymorphisms alter in vivo mRNA expression of p21. Lung Cancer 2003;40:259-266.
Draetta G, Eckstein J. Cdc25 protein phosphatases in cell proliferation. Biochim Biophys Acta 1997;1332:53-63.
William Taylor WR, Stark GR. Regulation of the G2/M transition by p53. Oncogene 2001;5:1803-1815.
Hwang BJ, Ford JM, Hanawalt PC, Chu G. Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair. Proc Natl Acad Sci USA 1999;96:424-428.
Helton ES, Chen X. p53 modulation of the DNA damage response. J Cell Biochem 2007;100:883-896.
Thierry Rossé T, Olivier R, Monney L, Rager M, Conus S, Fellay I, Jansen B, Borner C. Bcl-2 prolongs cell survival after Bax-induced release of cytochrome c. Nature 1998;391:496-499.
Sheikh MS, Burns TF, Huang Y, Wu GS, Amundson S, Brooks KS, Fornace AJ Jr, el-Deiry WS. p53 dependent and -independent Regulation of the Death Receptor KILLER/DR5 Gene Expression in Response to Genotoxic Stress and Tumor Necrosis Factor alpha. Cancer Res 1998;58:1593-1598.
Nishimori H, Shiratsuchi T, Urano T, Kimura Y, Kiyono K, Tatsumi K, Yoshida S, Ono M, Kuwano M, Nakamura Y, Tokino T. A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis. Oncogene 1997;18:2145-2150.
Van Meir EG, Polverini PJ, Chazin VR, Su Huang HJ, de Tribolet N, Cavenee WK. Release of an inhibitor of angiogenesis upon induction of wild type p53 expression in glioblastoma cells. Nat Genet 1994;8:171-176.
Harada H, Nakagawa K, Saito M, Kohno S, Nagato S, Furukawa K, Kumon Y, Hamada K, Ohnishi T. Introduction of wild-type p53 enhances thrombospondin-1 expression in human glioma cells. Cancer Lett 2003;191:109-1019.
Hussain SP, Amstad P, He P, Robles A, Lupold S, Kaneko I, Ichimiya M, Sengupta S, Mechanic L, Okamura S, Hofseth LJ, Moake M, Nagashima M, Forrester KS, Harris CC. p53-induced up-regulation of MnSOD and GPx but not catalase increases oxidative stress and apoptosis. Cancer Res 2004;64:2350-2356.
Yoon KA, Nakamura Y, Arakawa H. Identification of ALDH4 as a p53-inducible gene and its protective role in cellular stresses. J Hum Genet 2004;49:134-1340.
Budanov AV, Sablina AA, Feinstein E, Koonin EV, Chumakov PM. Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD. Science 2004;304:596-600.
Bensaad K, Tsuruta A, Selak MA, Vidal MN, Nakano K, Bartrons R, Gottlieb E, Vousden KH. TIGAR, a p53-inducible regulator of glycolysis and apoptosis. Cell 2006;126:107-120.
Bensaad K, Vousden KH. p53: new roles in metabolism. Trends Cell Biol 2007;17:286-291.
Lu X. p53: a heavily dictated dictator of life and death. Curr Opin Genet Dev 2005;15:27-33.
Erster S, Mihara M, Kim RH, Petrenko O, Moll UM. In vivo mitochondrial p53 translocation triggers a rapid first wave of cell death in response to DNA damage that can precede p53 target gene activation. Mol Cell Biol 2004;24:6728-41.
Murphy ME, Leu JI, George DL. p53 moves to mitochondria: a turn on the path to apoptosis. Cell Cycle 2004;3(7):836-9.
A.V. Vaseva, U.M. Moll. The mitochondrial p53 pathway. Biochimica et Biophysica Acta 2009;1787:414-420.
Taylor WR, DePrimo SE, Agarwal A, Agarwal ML, Schönthal AH, Katula KS, Stark GR. Mechanisms of G2 arrest in response to overexpression of p53.Mol Biol Cell 1999; 10:3607-36022.
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