Tumor spectrum analysis in p53-mutant mice
Abstract
Background The p53 tumor suppressor gene is mutated in a large percentage of human malignancies, including tumors of the colon, breast, lung and brain. Individuals who inherit one mutant allele of p53 are susceptible to a wide range of tumor types. The gene encodes a transcriptional regulator that may function in the cellular response to DNA damage. The construction of mouse strains carrying germline mutations of p53 facilitates analysis of the function of p53 in normal cells and tumorigenesis.Results In order to study the effects of p53 mutation in vivo, we have constructed a mouse strain carrying a germline disruption of the gene. This mutation removes approximately 40% of the coding capacity of p53 and completely eliminates synthesis of p53 protein. As observed previously for a different germline mutation of p53, animals homozygous for this p53 deletion mutation are viable but highly predisposed to malignancy. Heterozygous animals also have an increased cancer risk, although the distribution of tumor types in these animals differs from that in homozygous mutants. In most cases, tumorigenesis in heterozygous animals is accompanied by loss of the wild-type p53 allele.Conclusion We reaffirm that p53 function is not required for normal mouse development and conclude that p53 status can strongly influence tumor latency and tissue distribution.
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Tp53-knockout mice are born at normal Mendelian ratios and lack apparent phenotypic alterations but are prone to develop spontaneous tumours at around 6 months of age.
“Tp53 - knockout mice are born at normal Mendelian ratios and lack apparent phenotypic alterations but are prone to develop spontaneous tumours at around 6 months of age 127,128 .”
From Senescence and cancer — role and therapeutic opportunities (2022) · cites this paper as [128]
Mutations in p16, Rb, ARF and TP53 are frequently found in human cancers.
“Mutations in p16 , Rb , ARF and TP53 are frequently found in human cancers, and their tumour-suppressive roles have been confirmed in vivo using genetically modified mouse models [25 -29].”
From The role of cellular senescence and SASP in tumour microenvironment (2023) · cites this paper as [25]
The tumour-suppressive roles of p16, Rb, ARF and TP53 have been confirmed in vivo using genetically modified mouse models.
“Mutations in p16 , Rb , ARF and TP53 are frequently found in human cancers, and their tumour-suppressive roles have been confirmed in vivo using genetically modified mouse models [25 -29].”
From The role of cellular senescence and SASP in tumour microenvironment (2023) · cites this paper as [25]
Tumors that emerged in these models showed ALT activation, p53 mutation and/or diminished capacity to become fully malignant.
“Those tumors that did emerge showed activation of alternative lengthening of telomeres (ALT), mutation of p53 and/or a diminished capacity to achieve a fully malignant state (88,100).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [100]
Cites
Kastan, M. B., Zhan, Q., El-Deiry, W. S., Carrier, F., Jacks, T., Walsh, W. V., Plunkett, B. S., Vogelstein, B., & Fornace, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90593-2 · Cited by 3,047 · see citing works
Self-citationp53 is required for radiation-induced apoptosis in mouse thymocytes
Lowe, S. W., Schmitt, E. M., Smith, S. W., Osborne, B. A., & Jacks, T. (1993) · Nature · doi:10.1038/362847a0 · Cited by 2,864 · see citing works
Self-citationWild-type p53 activates transcription in vitro
Farmer, G., Bargonetti, J., Zhu, H., Friedman, P., Prywes, R., & Prives, C. (1992) · Nature · doi:10.1038/358083a0 · Cited by 579 · see citing works
Specific repression of TATA-mediated but not initiator-mediated transcription by wild-type p53
Mack, D. H., Vartikar, J., Pipas, J. M., & Laimins, L. A. (1993) · Nature · doi:10.1038/363281a0 · Cited by 322 · see citing works
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Sorted by citations
Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a
Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., & Lowe, S. W. (1997) · Cell · doi:10.1016/s0092-8674(00)81902-9 · Cited by 5,178 · see citing works
Hingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609 · see citing works
p21 in cancer: Intricate networks and multiple activities
Abbas, T., & Dutta, A. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2657 · Cited by 2,712 · see citing works
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse
Hingorani, S. R., Petricoin, E. F., Maitra, A., Rajapakse, V., King, C., Jacobetz, M. A., Ross, S., Conrads, T. P., Veenstra, T. D., Hitt, B. A., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00309-x · Cited by 2,471 · see citing works
Self-citationThe transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation
Wang, R., Dillon, C. P., Shi, L. Z., Milasta, S., Carter, R., Finkelstein, D., McCormick, L. L., Fitzgerald, P., Chi, H., Munger, J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.09.021 · Cited by 2,140 · see citing works
“Animals Hif1a and p53-null mice on the C57BL/6 background were purchased from the Jackson Laboratory (Jacks et al., 1994; Ryan et al., 2000) and Hif1a mice were crossed with ROSA26CreERT2 (de Luca et al.”
MethodMice Lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control
Deng, C., Zhang, P., Wade Harper, J., Elledge, S. J., & Leder, P. (1995) · Cell · doi:10.1016/0092-8674(95)90039-x · Cited by 2,113 · see citing works
Restoration of p53 function leads to tumour regression in vivo
Ventura, A., Kirsch, D. G., McLaughlin, M. E., Tuveson, D. A., Grimm, J., Lintault, L., Newman, J., Reczek, E. E., Weissleder, R., & Jacks, T. (2007) · Nature · doi:10.1038/nature05541 · Cited by 1,820 · see citing works
Self-citationcGAS surveillance of micronuclei links genome instability to innate immunity
Mackenzie, K. J., Carroll, P., Martin, C.-A., Murina, O., Fluteau, A., Simpson, D. J., Olova, N., Sutcliffe, H., Rainger, J. K., Leitch, A., et al. (2017) · Nature · doi:10.1038/nature23449 · Cited by 1,752 · see citing works
Tumor Suppression at the Mouse INK4a Locus Mediated by the Alternative Reading Frame Product p19
Kamijo, T., Zindy, F., Roussel, M. F., Quelle, D. E., Downing, J. R., Ashmun, R. A., Grosveld, G., & Sherr, C. J. (1997) · Cell · doi:10.1016/s0092-8674(00)80452-3 · Cited by 1,566 · see citing works
Pomerantz, J., Schreiber-Agus, N., Liégeois, N. J., Silverman, A., Alland, L., Chin, L., Potes, J., Chen, K., Orlow, I., Lee, H.-W., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81400-2 · Cited by 1,521 · see citing works
Demonstration of an interferon γ-dependent tumor surveillance system in immunocompetent mice
Kaplan, D. H., Shankaran, V., Dighe, A. S., Stockert, E., Aguet, M., Old, L. J., & Schreiber, R. D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7556 · Cited by 1,465 · see citing works
p53 mutant mice that display early ageing-associated phenotypes
Tyner, S. D., Venkatachalam, S., Choi, J., Jones, S., Ghebranious, N., Igelmann, H., Lu, X., Soron, G., Cooper, B., Brayton, C., et al. (2002) · Nature · doi:10.1038/415045a · Cited by 1,459 · see citing works
Programmed cell senescence during mammalian embryonic development
Muñoz-Espín, D., Cañamero, M., Maraver, A., Gómez-López, G., Contreras, J., Murillo-Cuesta, S., Rodríguez-Baeza, A., Varela-Nieto, I., Ruberte, J., Collado, M., et al. (2013) · Cell · doi:10.1016/j.cell.2013.10.019 · Cited by 1,428 · see citing works
Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53
de Oca Luna, R. M., Wagner, D. S., & Lozano, G. (1995) · Nature · doi:10.1038/378203a0 · Cited by 1,420 · see citing works
Mutant p53 gain of function in two mouse models of Li-Fraumeni syndrome
Olive, K. P., Tuveson, D. A., Ruhe, Z. C., Yin, B., Willis, N. A., Bronson, R. T., Crowley, D., & Jacks, T. (2004) · Cell · doi:10.1016/j.cell.2004.11.004 · Cited by 1,308 · see citing works
Butelli, E., Titta, L., Giorgio, M., Mock, H.-P., Matros, A., Peterek, S., Schijlen, E. G. W. M., Hall, R. D., Bovy, A. G., Luo, J., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt.1506 · Cited by 1,238 · see citing works
Somatic activation of the K-ras oncogene causes early onset lung cancer in mice
Johnson, L., Mercer, K., Greenbaum, D., Bronson, R. T., Crowley, D., Tuveson, D. A., & Jacks, T. (2001) · Nature · doi:10.1038/35074129 · Cited by 1,179 · see citing works
Self-citationGain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome
Lang, G. A., Iwakuma, T., Suh, Y.-A., Liu, G., Rao, V. A., Parant, J. M., Valentin-Vega, Y. A., Terzian, T., Caldwell, L. C., Strong, L. C., et al. (2004) · Cell · doi:10.1016/j.cell.2004.11.006 · Cited by 1,069 · see citing works
p53- and ATM-Dependent Apoptosis Induced by Telomeres Lacking TRF2
Karlseder, J., Broccoli, D., Dai, Y., Hardy, S., & de Lange, T. (1999) · Science · doi:10.1126/science.283.5406.1321 · Cited by 1,086 · see citing works
<i>ATR</i> disruption leads to chromosomal fragmentation and early embryonic lethality
Brown, E. J., & Baltimore, D. (2000) · Genes & Development · doi:10.1101/gad.14.4.397 · Cited by 951 · see citing works
Tumor Suppression in the Absence of p53-Mediated Cell-Cycle Arrest, Apoptosis, and Senescence
Li, T., Kon, N., Jiang, L., Tan, M., Ludwig, T., Zhao, Y., Baer, R., & Gu, W. (2012) · Cell · doi:10.1016/j.cell.2012.04.026 · Cited by 912 · see citing works
Marino, S., Vooijs, M., van der Gulden, H., Jonkers, J., & Berns, A. (2000) · Genes & Development · doi:10.1101/gad.14.8.994 · Cited by 920 · see citing works
p53-Dependent apoptosis suppresses tumor growth and progression in vivo
Symonds, H., Krall, L., Remington, L., Saenz-Robles, M., Lowe, S., Jacks, T., & Van Dyke, T. (1994) · Cell · doi:10.1016/0092-8674(94)90534-7 · Cited by 880 · see citing works
Self-citationSIRT1 redistribution on chromatin promotes genomic stability but alters gene expression during aging
Oberdoerffer, P., Michan, S., McVay, M., Mostoslavsky, R., Vann, J., Park, S.-K., Hartlerode, A., Stegmuller, J., Hafner, A., Loerch, P., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.025 · Cited by 852 · see citing works
Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis
Eischen, C. M., Weber, J. D., Roussel, M. F., Sherr, C. J., & Cleveland, J. L. (1999) · Genes & Development · doi:10.1101/gad.13.20.2658 · Cited by 819 · see citing works
Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice
Collins, M. A., Bednar, F., Zhang, Y., Brisset, J.-C., Galbán, S., Galbán, C. J., Rakshit, S., Flannagan, K. S., Adsay, N. V., & Pasca di Magliano, M. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59227 · Cited by 770 · see citing works
Senescence and cancer — role and therapeutic opportunities
Schmitt, C. A., Wang, B., & Demaria, M. (2022) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-022-00668-4 · Cited by 794 · see citing works
Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation
Jackson-Grusby, L., Beard, C., Possemato, R., Tudor, M., Fambrough, D., Csankovszki, G., Dausman, J., Lee, P., Wilson, C., Lander, E., et al. (2001) · Nature Genetics · doi:10.1038/83730 · Cited by 694 · see citing works
DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion
Celli, G. B., & de Lange, T. (2005) · Nature Cell Biology · doi:10.1038/ncb1275 · Cited by 623 · see citing works
Tissue damage and senescence provide critical signals for cellular reprogramming in vivo
Mosteiro, L., Pantoja, C., Alcazar, N., Marión, R. M., Chondronasiou, D., Rovira, M., Fernandez-Marcos, P. J., Muñoz-Martin, M., Blanco-Aparicio, C., Pastor, J., et al. (2016) · Science · doi:10.1126/science.aaf4445 · Cited by 589 · see citing works
Fisher, G. H., Wellen, S. L., Klimstra, D., Lenczowski, J. M., Tichelaar, J. W., Lizak, M. J., Whitsett, J. A., Koretsky, A., & Varmus, H. E. (2001) · Genes & Development · doi:10.1101/gad.947701 · Cited by 582 · see citing works
The INK4A/ARF locus and its two gene products.
Sharpless, N. E., & DePinho, R. A. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)80004-5 · Cited by 533 · see citing works
Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance
Brown, E. J., & Baltimore, D. (2003) · Genes & Development · doi:10.1101/gad.1067403 · Cited by 511 · see citing works
Coping with stress: multiple ways to activate p53
Horn, H. F., & Vousden, K. H. (2007) · Oncogene · doi:10.1038/sj.onc.1210263 · Cited by 522 · see citing works
Parant, J., Chavez-Reyes, A., Little, N. A., Yan, W., Reinke, V., Jochemsen, A. G., & Lozano, G. (2001) · Nature Genetics · doi:10.1038/ng714 · Cited by 517 · see citing works
Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others
Sabapathy, K., & Lane, D. P. (2018) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.151 · Cited by 517 · see citing works
p53 and E2f: partners in life and death
Polager, S., & Ginsberg, D. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2718 · Cited by 498 · see citing works
Different telomere damage signaling pathways in human and mouse cells
Smogorzewska, A., & de Lange, T. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf433 · Cited by 482 · see citing works
Politi, K., Zakowski, M. F., Fan, P.-D., Schonfeld, E. A., Pao, W., & Varmus, H. E. (2006) · Genes & Development · doi:10.1101/gad.1417406 · Cited by 478 · see citing works
The p53 network: cellular and systemic DNA damage responses in aging and Cancer
Reinhardt, H. C., & Schumacher, B. (2012) · Trends in Genetics · doi:10.1016/j.tig.2011.12.002 · Cited by 458 · see citing works
INK4a/ARF mutations accelerate lymphomagenesis and promote chemoresistance by disabling p53
Schmitt, C. A., McCurrach, M. E., de Stanchina, E., Wallace-Brodeur, R. R., & Lowe, S. W. (1999) · Genes & Development · doi:10.1101/gad.13.20.2670 · Cited by 458 · see citing works
An Attempt to Prevent Senescence: A Mitochondrial Approach
Skulachev, V. P., Anisimov, V. N., Antonenko, Y. N., Bakeeva, L. E., Chernyak, B. V., Erichev, V. P., Filenko, O. F., Kalinina, N. I., Kapelko, V. I., Kolosova, N. G., et al. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.12.008 · Cited by 430 · see citing works
p53 modifications: exquisite decorations of the powerful guardian
Liu, Y., Tavana, O., & Gu, W. (2019) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjz060 · Cited by 392 · see citing works
Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors
Murga, M., Campaner, S., Lopez-Contreras, A. J., Toledo, L. I., Soria, R., Montaña, M. F., D'Artista, L., Schleker, T., Guerra, C., Garcia, E., et al. (2011) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2189 · Cited by 381 · see citing works
The pathological response to DNA damage does not contribute to p53-mediated tumour suppression
Christophorou, M. A., Ringshausen, I., Finch, A. J., Swigart, L. B., & Evan, G. I. (2006) · Nature · doi:10.1038/nature05077 · Cited by 382 · see citing works
Jackson, J. G., Pant, V., Li, Q., Chang, L. L., Quintás-Cardama, A., Garza, D., Tavana, O., Yang, P., Manshouri, T., Li, Y., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.04.027 · Cited by 329 · see citing works
MDM4 is a key therapeutic target in cutaneous melanoma
Gembarska, A., Luciani, F., Fedele, C., Russell, E. A., Dewaele, M., Villar, S., Zwolinska, A., Haupt, S., de Lange, J., Yip, D., et al. (2012) · Nature Medicine · doi:10.1038/nm.2863 · Cited by 327 · see citing works
Liu, G., Parant, J. M., Lang, G., Chau, P., Chavez-Reyes, A., El-Naggar, A. K., Multani, A., Chang, S., & Lozano, G. (2004) · Nature Genetics · doi:10.1038/ng1282 · Cited by 325 · see citing works
Mutant p53 in Cancer: Accumulation, Gain-of-Function, and Therapy
Yue, X., Zhao, Y., Xu, Y., Zheng, M., Feng, Z., & Hu, W. (2017) · Journal of Molecular Biology · doi:10.1016/j.jmb.2017.03.030 · Cited by 308 · see citing works
Migliorini, D., Denchi, E. L., Danovi, D., Jochemsen, A., Capillo, M., Gobbi, A., Helin, K., Pelicci, P. G., & Marine, J.-C. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.15.5527-5538.2002 · Cited by 313 · see citing works
The p53 family in differentiation and tumorigenesis
Stiewe, T. (2007) · Nature Reviews Cancer · doi:10.1038/nrc2072 · Cited by 306 · see citing works
Caspase-14 protects against epidermal UVB photodamage and water loss
Denecker, G., Hoste, E., Gilbert, B., Hochepied, T., Ovaere, P., Lippens, S., Van den Broecke, C., Van Damme, P., D'Herde, K., Hachem, J.-P., et al. (2007) · Nature Cell Biology · doi:10.1038/ncb1597 · Cited by 298 · see citing works
Mdm4 and Mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells <i>in vivo</i>
Francoz, S., Froment, P., Bogaerts, S., De Clercq, S., Maetens, M., Doumont, G., Bellefroid, E., & Marine, J.-C. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508476103 · Cited by 260 · see citing works
Effects of genetic background on tumorigenesis in <i>p53</i>‐deficient mice
Donehower, L. A., Harvey, M., Vogel, H., McArthur, M. J., Montgomery, C. A., Park, S. H., Thompson, T., Ford, R. J., & Bradley, A. (1995) · Molecular Carcinogenesis · doi:10.1002/mc.2940140105 · Cited by 252 · see citing works
Ribonuclease H2 mutations induce a cGAS/STING‐dependent innate immune response
Mackenzie, K. J., Carroll, P., Lettice, L., Tarnauskaitė, Ž., Reddy, K., Dix, F., Revuelta, A., Abbondati, E., Rigby, R. E., Rabe, B., et al. (2016) · The EMBO Journal · doi:10.15252/embj.201593339 · Cited by 248 · see citing works
Mendrysa, S. M., McElwee, M. K., Michalowski, J., O'Leary, K. A., Young, K. M., & Perry, M. E. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.2.462-473.2003 · Cited by 234 · see citing works
Lundgren, K., Montes de Oca Luna, R., McNeill, Y. B., Emerick, E. P., Spencer, B., Barfield, C. R., Lozano, G., Rosenberg, M. P., & Finlay, C. A. (1997) · Genes & Development · doi:10.1101/gad.11.6.714 · Cited by 235 · see citing works
Genetically engineered pigs as models for human disease
Perleberg, C., Kind, A., & Schnieke, A. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.030783 · Cited by 222 · see citing works
Cell type-specific effects of <i>Rb</i> deletion in the murine retina
MacPherson, D., Sage, J., Kim, T., Ho, D., McLaughlin, M. E., & Jacks, T. (2004) · Genes & Development · doi:10.1101/gad.1203304 · Cited by 222 · see citing works
Self-citationCellular senescence and apoptosis: how cellular responses might influence aging phenotypes
Campisi, J. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(02)00152-3 · Cited by 218 · see citing works
Cancer predisposition and hematopoietic failure in <i> Rad50 <sup>S/S</sup> </i> mice
Bender, C. F., Sikes, M. L., Sullivan, R., Huye, L. E., Le Beau, M. M., Roth, D. B., Mirzoeva, O. K., Oltz, E. M., & Petrini, J. H. J. (2002) · Genes & Development · doi:10.1101/gad.1007902 · Cited by 213 · see citing works
Wide spectrum of tumors in knock‐in mice carrying a Cdk4 protein insensitive to INK4 inhibitors
Sotillo, R., Dubus, P., Martn, J., de la Cueva, E., Ortega, S., Malumbres, M., & Barbacid, M. (2001) · The EMBO Journal · doi:10.1093/emboj/20.23.6637 · Cited by 208 · see citing works
A Murine Model of Nijmegen Breakage Syndrome
Williams, B. R., Mirzoeva, O. K., Morgan, W. F., Lin, J., Dunnick, W., & Petrini, J. H. J. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00763-7 · Cited by 208 · see citing works
Self-citationSteele-Perkins, G., Fang, W., Yang, X.-H., Van Gele, M., Carling, T., Gu, J., Buyse, I. M., Fletcher, J. A., Liu, J., Bronson, R., et al. (2001) · Genes & Development · doi:10.1101/gad.870101 · Cited by 208 · see citing works
Pantoja, C., & Serrano, M. (1999) · Oncogene · doi:10.1038/sj.onc.1202880 · Cited by 201 · see citing works
Intact p53-Dependent Responses in miR-34–Deficient Mice
Concepcion, C. P., Han, Y.-C., Mu, P., Bonetti, C., Yao, E., D'Andrea, A., Vidigal, J. A., Maughan, W. P., Ogrodowski, P., & Ventura, A. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002797 · Cited by 197 · see citing works
Reduction in glutathione peroxidase 4 increases life span through increased sensitivity to apoptosis
Ran, Q., Liang, H., Ikeno, Y., Qi, W., Prolla, T. A., Roberts, L. J., Wolf, N., VanRemmen, H., & Richardson, A. (2007) · The Journals of Gerontology Series A: Biological Sciences and Medical Sciences · doi:10.1093/gerona/62.9.932 · Cited by 195 · see citing works
Keyes, W. M., Pecoraro, M., Aranda, V., Vernersson-Lindahl, E., Li, W., Vogel, H., Guo, X., Garcia, E. L., Michurina, T. V., Enikolopov, G., et al. (2011) · Cell Stem Cell · doi:10.1016/j.stem.2010.12.009 · Cited by 193 · see citing works
The p53 inhibitors MDM2/MDMX complex is required for control of p53 activity in vivo
Huang, L., Yan, Z., Liao, X., Li, Y., Yang, J., Wang, Z.-G., Zuo, Y., Kawai, H., Shadfan, M., Ganapathy, S., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102309108 · Cited by 193 · see citing works
Mutations in the <i>WRN</i> Gene in Mice Accelerate Mortality in a p53-Null Background
Lombard, D. B., Beard, C., Johnson, B., Marciniak, R. A., Dausman, J., Bronson, R., Buhlmann, J. E., Lipman, R., Curry, R., Sharpe, A., et al. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.9.3286-3291.2000 · Cited by 187 · see citing works
Self-citationMosteiro, L., Pantoja, C., de Martino, A., & Serrano, M. (2018) · Aging Cell · doi:10.1111/acel.12711 · Cited by 182 · see citing works
Tumor Stroma-Derived TGF-β Limits Myc-Driven Lymphomagenesis via Suv39h1-Dependent Senescence
Reimann, M., Lee, S., Loddenkemper, C., Dörr, J. R., Tabor, V., Aichele, P., Stein, H., Dörken, B., Jenuwein, T., & Schmitt, C. A. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.12.043 · Cited by 184 · see citing works
Le, O. N. L., Rodier, F., Fontaine, F., Coppe, J., Campisi, J., DeGregori, J., Laverdière, C., Kokta, V., Haddad, E., & Beauséjour, C. M. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00567.x · Cited by 168 · see citing works
Endocrine-Exocrine Signaling Drives Obesity-Associated Pancreatic Ductal Adenocarcinoma
Chung, K. M., Singh, J., Lawres, L., Dorans, K. J., Garcia, C., Burkhardt, D. B., Robbins, R., Bhutkar, A., Cardone, R., Zhao, X., et al. (2020) · Cell · doi:10.1016/j.cell.2020.03.062 · Cited by 150 · see citing works
Self-citationDual Inactivation of RB and p53 Pathways in RAS-Induced Melanomas
Bardeesy, N., Bastian, B. C., Hezel, A., Pinkel, D., DePinho, R. A., & Chin, L. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.6.2144-2153.2001 · Cited by 166 · see citing works
Current understanding of the role and targeting of tumor suppressor p53 in glioblastoma multiforme
England, B., Huang, T., & Karsy, M. (2013) · Tumor Biology · doi:10.1007/s13277-013-0871-3 · Cited by 163 · see citing works
JunB can substitute for Jun in mouse development and cell proliferation
Passegué, E., Jochum, W., Behrens, A., Ricci, R., & Wagner, E. F. (2002) · Nature Genetics · doi:10.1038/ng790 · Cited by 162 · see citing works
The Central Sirtuin 1/p53 Pathway Is Essential for the Orexigenic Action of Ghrelin
Velásquez, D. A., Martínez, G., Romero, A., Vázquez, M. J., Boit, K. D., Dopeso-Reyes, I. G., López, M., Vidal, A., Nogueiras, R., & Diéguez, C. (2011) · Diabetes · doi:10.2337/db10-0802 · Cited by 161 · see citing works
Ser18 and 23 phosphorylation is required for p53‐dependent apoptosis and tumor suppression
Chao, C., Herr, D., Chun, J., & Xu, Y. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601167 · Cited by 158 · see citing works
Yu, Y., Schleich, K., Yue, B., Ji, S., Lohneis, P., Kemper, K., Silvis, M. R., Qutob, N., van Rooijen, E., Werner-Klein, M., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.01.002 · Cited by 156 · see citing works
Irradiation selects for p53-deficient hematopoietic progenitors.
Marusyk, A., Porter, C. C., Zaberezhnyy, V., & DeGregori, J. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000324 · Cited by 151 · see citing works
The role of cellular senescence and SASP in tumour microenvironment
Takasugi, M., Yoshida, Y., Hara, E., & Ohtani, N. (2023) · The FEBS Journal · doi:10.1111/febs.16381 · Cited by 144 · see citing works
Tissue-specific differences of p53 inhibition by Mdm2 and Mdm4
Grier, J. D., Xiong, S., Elizondo-Fraire, A. C., Parant, J. M., & Lozano, G. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.1.192-198.2006 · Cited by 149 · see citing works
Hdmx protein stability is regulated by the ubiquitin ligase activity of Mdm2
de Graaf, P., Little, N. A., Ramos, Y. F. M., Meulmeester, E., Letteboer, S. J. F., & Jochemsen, A. G. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m213034200 · Cited by 143 · see citing works
Efeyan, A., Ortega-Molina, A., Velasco-Miguel, S., Herranz, D., Vassilev, L. T., & Serrano, M. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-0200 · Cited by 140 · see citing works
p21 Both Attenuates and Drives Senescence and Aging in BubR1 Progeroid Mice
Baker, D. J., Weaver, R. L., & van Deursen, J. M. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.03.028 · Cited by 130 · see citing works
The p53 pathway in hematopoiesis: lessons from mouse models, implications for humans
Pant, V., Quintás-Cardama, A., & Lozano, G. (2012) · Blood · doi:10.1182/blood-2012-05-356014 · Cited by 129 · see citing works
A High-Frequency Regulatory Polymorphism in the p53 Pathway Accelerates Tumor Development
Post, S. M., Quintás-Cardama, A., Pant, V., Iwakuma, T., Hamir, A., Jackson, J. G., Maccio, D. R., Bond, G. L., Johnson, D. G., Levine, A. J., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.07.010 · Cited by 127 · see citing works
Defective apoptosis and B-cell lymphomas in mice with p53 point mutation at Ser 23
MacPherson, D., Kim, J., Kim, T., Rhee, B. K., van Oostrom, C. T., DiTullio, R. A., Venere, M., Halazonetis, T. D., Bronson, R., de Vries, A., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600363 · Cited by 124 · see citing works
Zeron-Medina, J., Wang, X., Repapi, E., Campbell, M. R., Su, D., Castro-Giner, F., Davies, B., Peterse, E. F. P., Sacilotto, N., Walker, G. J., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.017 · Cited by 118 · see citing works
Increased Sensitivity to UV Radiation in Mice with a p53 Point Mutation at Ser389
Bruins, W., Zwart, E., Attardi, L. D., Iwakuma, T., Hoogervorst, E. M., Beems, R. B., Miranda, B., van Oostrom, C. T. M., van den Berg, J., van den Aardweg, G. J., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.20.8884-8894.2004 · Cited by 121 · see citing works
Self-citationHaploinsufficiency of <i>Mdm2</i> and <i>Mdm4</i> in Tumorigenesis and Development
Terzian, T., Wang, Y., Van Pelt, C. S., Box, N. F., Travis, E. L., & Lozano, G. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00555-06 · Cited by 116 · see citing works
Gannon, H. S., Woda, B. A., & Jones, S. N. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.04.011 · Cited by 105 · see citing works
Cellular lifespan and senescence signaling in embryonic stem cells
Miura, T., Mattson, M. P., & Rao, M. S. (2004) · Aging Cell · doi:10.1111/j.1474-9728.2004.00134.x · Cited by 102 · see citing works
Mutation of Mouse p53 Ser23 and the Response to DNA Damage
Wu, Z., Earle, J., Saito, S., Anderson, C. W., Appella, E., & Xu, Y. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.8.2441-2449.2002 · Cited by 103 · see citing works
Huang, Y., Liu, N., Liu, J., Liu, Y., Zhang, C., Long, S., Luo, G., Zhang, L., & Zhang, Y. (2019) · Cell Cycle · doi:10.1080/15384101.2019.1688951 · Cited by 94 · see citing works
Green, M. R., Vicente-Dueñas, C., Romero-Camarero, I., Long Liu, C., Dai, B., González-Herrero, I., García-Ramírez, I., Alonso-Escudero, E., Iqbal, J., Chan, W. C., et al. (2014) · Nature Communications · doi:10.1038/ncomms4904 · Cited by 88 · see citing works
Roles of HAUSP-mediated p53 regulation in central nervous system development
Kon, N., Zhong, J., Kobayashi, Y., Li, M., Szabolcs, M., Ludwig, T., Canoll, P. D., & Gu, W. (2011) · Cell Death & Differentiation · doi:10.1038/cdd.2011.12 · Cited by 79 · see citing works
Towards an understanding of the role of p53 in adrenocortical carcinogenesis
Wasserman, J. D., Zambetti, G. P., & Malkin, D. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.09.010 · Cited by 84 · see citing works
Validation of MdmX as a therapeutic target for reactivating p53 in tumors
Garcia, D., Warr, M. R., Martins, C. P., Brown Swigart, L., Passegué, E., & Evan, G. I. (2011) · Genes & Development · doi:10.1101/gad.16722111 · Cited by 83 · see citing works
- Authors
- Jacks, T., Remington, L., Williams, B. O., Schmitt, E. M., Halachmi, S., Bronson, R. T., & Weinberg, R. A.
- Affiliations
- Massachusetts Institute of Technology (US)
- Tufts University (US)
- Whitehead Institute for Biomedical Research (US)
- Corresponding author
- Jacks, Tyler
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 1994-01
- Volume
- 4
- Issue
- 1
- Pages
- 1-7
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2088740611
- Cited by
- 2,051
- References
- 4
- Citations by year
- 2026: 17 · 2025: 33 · 2024: 51 · 2023: 46 · 2022: 35 · 2021: 58 · 2020: 63 · 2019: 44 · 2018: 61 · 2017: 57 · 2016: 66 · 2015: 51 · 2014: 75 · 2013: 72 · 2012: 102
- FWCI
- 17.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institutes of Health (5r35ca039826-10)
- National Cancer Institute (5R35 CA39826)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- p53, tumor suppressor, germline mutations, p53 knockout mice, tumor spectrum, tumor latency, heterozygous carriers, cancer susceptibility, DNA damage response, transcriptional regulation
- MeSH terms
- Alleles, Animals, Base Sequence, Chimera, Chromosome Deletion, Crosses, Genetic, DNA Damage, Female, Humans, Male, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Neoplasms, Experimental, Polymerase Chain Reaction, Genes, p53, Tumor Suppressor Protein p53, Li-Fraumeni Syndrome, Sequence Deletion, DNA Primers, Mice
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