Cited by 1,280Cancer-related Molecular PathwaysDevelopmental Biology and Gene RegulationCell death mechanisms and regulation

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Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53

Jones, Stephen N., Roe, Amy E., Donehower, Lawrence A., Bradley, Allan·1995·Nature

DOI 10.1038/378206a0

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Abstract

The Mdm2 proto-oncogene was originally identified as one of several genes contained on a mouse double minute chromosome present in a transformed derivative of 3T3 cells. Overexpression of Mdm2 can immortalize primary cultures of rodent fibroblasts. Human MDM2 is amplified in 30-40% of sarcomas, and is overexpressed in leukaemic cells. The Mdm2 oncoprotein forms a complex with the p53 tumour-suppressor protein and inhibits p53-mediated transregulation of gene expression. Because Mdm2 expression increases in response to p53, Mdm2-p53 binding may autoregulate Mdm2 expression and modulate the activity of p53 in the cell. We have created Mdm2-null and Mdm2/p53-null mice to determine whether Mdm2 possesses developmental functions in addition to the ability to complex with p53, and to investigate the biological role of Mdm2-p53 complex formation in development. Mice deficient for Mdm2 die early in development. In contrast, mice deficient for both Mdm2 and p53 develop normally and are viable. These results suggest that a critical role of Mdm2 in development is the regulation of p53 function.

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p53 Mutations in Human Cancers
Hollstein, M., Sidransky, D., Vogelstein, B., & Harris, C. C. (1991) · Science · doi:10.1126/science.1905840 · Cited by 8,018
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
Donehower, L. A., Harvey, M., Slagle, B. L., McArthur, M. J., Montgomery, C. A., Butel, J. S., & Bradley, A. (1992) · Nature · doi:10.1038/356215a0 · Cited by 4,649
Self-citation
Participation of p53 protein in the cellular response to DNA damage.
Kastan, M. B., Onyekwere, O. C., Sidransky, D., Vogelstein, B., & Craig, R. W. (1991) · PubMed · Cited by 3,761
The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation
Momand, J., Zambetti, G. P., Olson, D. C., George, D., & Levine, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90644-r · Cited by 3,113
Amplification of a gene encoding a p53-associated protein in human sarcomas
Oliner, J. D., Kinzler, K. W., Meltzer, P. S., George, D. L., & Vogelstein, B. (1992) · Nature · doi:10.1038/358080a0 · Cited by 1,949
The p53-mdm-2 autoregulatory feedback loop.
Wu, X., Bayle, J. H., Olson, D., & Levine, A. J. (1993) · Genes & Development · doi:10.1101/gad.7.7a.1126 · Cited by 1,801
The Atlas of Mouse Development
Kaufman, M. H. (1992) · Medical Entomology and Zoology · Cited by 1,750
Disruption of the proto-oncogene int-2 in mouse embryo-derived stem cells: A general strategy for targeting mutations to non-selectable genes
Mansour, S. L., Thomas, K. R., & Capecchi, M. R. (1988) · Nature · doi:10.1038/336348a0 · Cited by 1,683
The atlas of mouse development
Beddington, R. S. P. (1993) · Trends in Genetics · doi:10.1016/0168-9525(93)90071-o · Cited by 1,416
α-lnhibin is a tumour-suppressor gene with gonadal specificity in mice
Matzuk, M. M., Finegold, M. J., Su, J.-G. J., Hsueh, A. J. W., & Bradley, A. (1992) · Nature · doi:10.1038/360313a0 · Cited by 893
Self-citation

Flagged first, then by citations

Show all 24 references

Research works printed but not linked: 5

Juven, T., Barak, Y., Zauberman, A., George, D. & Oren, M. Oncogene 8, 3411–3416 (1993).
Snow, M. H. L. J. Embryol. exp. Morph. 42, 293–303 (1977).
Baker, S. J., Markowitz, S., Fearon, E. R., Willson, J. K. V. & Vogelstein, B. Science 253, 49–53 (1990).
Kastan, M. B., Onyekwere, O., Sidransky, D., Vogelstein, B. & Craig, R. W. Cancer Res. 51, 6304–6311 (1991).
Olson, D. C. et al. Oncogene 8, 2353–2360 (1993).

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Li, M., Gou, H., Tripathi, B. K., Huang, J. L., Jiang, S., Dubois, W., Waybright, T., Lei, M., Shi, J., Zhou, M., et al. (2015) · Cell stem cell · doi:10.1016/j.stem.2015.04.002 · Cited by 105
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Badciong, J. C., & Haas, A. L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208593200 · Cited by 108
Collagenase and gelatinase activities in bronchoalveolar lavage fluids during bleomycin-induced lung injury
Bakowska, J., & Adamson, I. Y. R. (1998) · The Journal of Pathology · doi:10.1002/(sici)1096-9896(199807)185:3 · Cited by 47
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Wang, H., Nan, L., Yu, D. S., Agrawal, S., & Zhang, R. (2001) · PubMed · Cited by 106
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Chandler, D. S., Singh, R. K., Caldwell, L. C., Bitler, J. L., & Lozano, G. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4271 · Cited by 108
A Runx2 threshold for the cleidocranial dysplasia phenotype
Lou, Y., Javed, A., Hussain, S., Colby, J. M., Frederick, D., Pratap, J., Xie, R., Gaur, T., van Wijnen, A. J., Jones, S. N., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn383 · Cited by 105
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Canman, C. E., & Kastan, M. B. (1997) · Advances in pharmacology · doi:10.1016/s1054-3589(08)61068-6 · Cited by 106
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Jacks, T. (1996) · Annual Review of Genetics · doi:10.1146/annurev.genet.30.1.603 · Cited by 105
Restoration of p53 to limit tumor growth
Wang, W., & El‐Deiry, W. S. (2008) · Current Opinion in Oncology · doi:10.1097/cco.0b013e3282f31d6f · Cited by 105
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
“Although p53-null mice are viable (Donehower et al., 1992; Jacks et al., 1994), mice lacking mdm2, which is a negative regulator of p53, die at an early embryo stage (Jones et al., 1995; Montes de Oca Luna et al., 1995).”
Background
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Phesse, T. J., Myant, K., Cole, A. M., Ridgway, R. A., Pearson, H. B., Muncan, V., BRINK, G. R. V. D., Vousden, K. H., Sears, R. C., Vassilev, L. T., et al. (2014) · Cell Death and Differentiation · doi:10.1038/cdd.2014.15 · Cited by 102
MDM2 antagonists as a novel treatment option for acute myeloid leukemia: perspectives on the therapeutic potential of idasanutlin (RG7388)
Khurana, A., & Shafer, D. A. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s172315 · Cited by 111
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Tang, S. J., Hoodless, P. A., Lü, Z., Breitman, M. L., McInnes, R. R., Wrana, J. L., & Buchwald, M. (1998) · Development · doi:10.1242/dev.125.10.1877 · Cited by 104
Analysis of the degradation function of Mdm2.
Kubbutat, M. H. G., Ludwig, R., Levine, A. J., & Vousden, K. H. (1999) · PubMed · Cited by 102
The Role of the Apoptotic Machinery in Tumor SuppressionPreprint
Delbridge, A. R. D., Valente, L. J., & Strasser, A. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a008789 · Cited by 106
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Ungewitter, E. K., & Scrable, H. J. (2010) · Genes & Development · doi:10.1101/gad.1987810 · Cited by 101
Discovery of Mdm2-MdmX E3 Ligase Inhibitors Using a Cell-Based Ubiquitination Assay
Herman, A. G., Hayano, M., Poyurovsky, M. V., Shimada, K., Skouta, R., Prives, C., & Stockwell, B. R. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0104 · Cited by 100
“This relationship is illustrated by the rescue of embryonic lethality of Mdm2 mice by the concomitant deletion of p53 (11, 12).”
Endoplasmic Reticulum Stress Accelerates p53 Degradation by the Cooperative Actions of Hdm2 and Glycogen Synthase Kinase 3β
Pluquet, O., Qu, L., Baltzis, D., & Koromilas, A. E. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9392-9405.2005 · Cited by 106
Tumour suppressors: A developing role for p53?
Hall, P. A., & Lane, D. P. (1997) · Current Biology · doi:10.1016/s0960-9822(97)70074-5 · Cited by 101
Targeting of C-Terminal Binding Protein (CtBP) by ARF Results in p53-Independent Apoptosis
Paliwal, S., Pande, S., Kovi, R. C., Sharpless, N. E., Bardeesy, N. M., & Grossman, S. R. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.6.2360-2372.2006 · Cited by 104
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Kruse, J.-P., & Gu, W. J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805658200 · Cited by 101
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Sharp, A. N., Heazell, A. E. P., Baczyk, D., Dunk, C., Lacey, H. A., Jones, C. J. P., Perkins, J., Kingdom, J. C., Baker, P. N., & Crocker, I. P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087621 · Cited by 98
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Patel, S., & Player, M. R. (2008) · Expert Opinion on Investigational Drugs · doi:10.1517/13543780802493366 · Cited by 101
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Tóth, A., Nickson, P., Qin, L. L., & Erhardt, P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509630200 · Cited by 97
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Daujat, S., NEEL, H., & PIETTE, J. (2001) · Trends in Genetics · doi:10.1016/s0168-9525(01)02369-1 · Cited by 97
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Steinman, H. A., Burstein, E., Lengner, C., Gosselin, J., Pihan, G., Duckett, C. S., & Jones, S. N. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m305966200 · Cited by 96
Self-citation
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O’Neill, C. (2008) · Human Reproduction Update · doi:10.1093/humupd/dmn002 · Cited by 97
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“This problem cannot be addressed genetically because of the early lethality of mdm2-knockout embryos (Jones et al., 1995; Montes de Oca Luna et al., 1995) and because of minor changes in Mdm2 mRNA levels in livers of mdm2 hypomorphic mice 1447RESEARCH ARTICLECell survival by Met requires mTOR-Mdm2…”
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Perry, M. E. (2004) · Molecular Cancer Research · doi:10.1158/1541-7786.9.2.1 · Cited by 96
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Boyd, M. T., Vlatković, N., & Haines, D. S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004252200 · Cited by 93
mdm2: a bridge over the two tumour suppressors, p53 and Rb
Yap, D., Hsieh, J.-K., Chan, F., & Lü, X. (1999) · Oncogene · doi:10.1038/sj.onc.1202954 · Cited by 93
Mouse Models of p53 FunctionsPreprint
Lozano, G. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001115 · Cited by 97
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Xirodimas, D. P., Chisholm, J., Desterro, J. M. S., Lane, D. P., & Hay, R. T. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)03310-0 · Cited by 94
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Bartel, F., Schulz, J., Böhnke, A., Blümke, K., Kappler, M., Bache, M., Schmidt, H., Würl, P., Taubert, H. W., & Hauptmann, S. (2005) · International Journal of Cancer · doi:10.1002/ijc.21206 · Cited by 93
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Saxena, A. D., Rorie, C. J., Dimitrova, D. D., Daniely, Y., & Borowiec, J. A. (2006) · Oncogene · doi:10.1038/sj.onc.1209714 · Cited by 94
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Developmental Studies of Brca1 and Brca2 Knock-Out Mice
Hakem, R., de la Pompa, J. L., & Mak, T. W. (1998) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1023/a:1018792200700 · Cited by 91
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Loughran, Ö., & Thangue, N. B. L. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.6.2186-2197.2000 · Cited by 90
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Zhao, Y., Bernard, D., & Wang, S. (2013) · Biodiscovery · doi:10.7750/biodiscovery.2013.8.4 · Cited by 91
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Chen, D., Zhang, J., Li, M., Rayburn, E. R., Wang, H., & Zhang, R. (2008) · EMBO Reports · doi:10.1038/embor.2008.231 · Cited by 89
A Genetic Approach to Mapping the p53 Binding Site in the MDM2 Protein
Freedman, D. A., Epstein, C. B., Roth, J. C., & Levine, A. J. (1997) · Molecular Medicine · doi:10.1007/bf03401678 · Cited by 91
The contribution of the acidic domain of MDM2 to p53 and MDM2 stability
Argentini, M., Barboule, N., & Wasylyk, B. (2001) · Oncogene · doi:10.1038/sj.onc.1204241 · Cited by 90
The p53 Tumor Suppressor Protein Does Not Regulate Expression of Its Own Inhibitor, MDM2, Except under Conditions of Stress
Mendrysa, S. M., & Perry, M. E. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.6.2023-2030.2000 · Cited by 87
Apoptosis and the cell cycle
Fotedar, R., Diederich, L., & Fotedar, A. (1996) · Springer eBooks · doi:10.1007/978-1-4615-5873-6_15 · Cited by 91
Aggregation and Prion-Like Properties of Misfolded Tumor Suppressors: Is Cancer a Prion Disease?Preprint
da Costa, D. C. F., de Oliveira, G. A. P., Cino, E. A., Soares, I. N., Rangel, L. P., & Silva, J. L. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a023614 · Cited by 89
p53/MDM2 signaling pathway in aging, senescence and tumorigenesis
Huang, Y., Che, X., Wang, P., & Qu, X. (2024) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2024.05.001 · Cited by 99
M‐CAM expression as marker of poor prognosis in epithelial ovarian cancer
Aldovini, D., Demichelis, F., Doglioni, C., Vizio, D. D., Galligioni, E., Brugnara, S., Zeni, B., Griso, C., Pegoraro, C., Zannoni, M., et al. (2006) · International Journal of Cancer · doi:10.1002/ijc.22082 · Cited by 88
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Barboza, J., Iwakuma, T., Terzian, T., El‐Naggar, A. K., & Lozano, G. (2008) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-07-2079 · Cited by 91
From p63 to p53 across p73
Strano, S., Rossi, M., Fontemaggi, G., Munarriz, E. R., Soddu, S., Sacchi, A., & Blandino, G. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02119-6 · Cited by 87
Mdm2–p53 signaling regulates epidermal stem cell senescence and premature aging phenotypes in mouse skin
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Self-citation
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Wei, S., Schell, J. R., Chocrón, E. S., Varmazyad, M., Xu, G., Chen, W. H., Martinez, G. M., Dong, F. F., Sreenivas, P., Trevino, R., et al. (2024) · Science Advances · doi:10.1126/sciadv.ado1463 · Cited by 90
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Stommel, J. M., & Wahl, G. M. (2005) · Cell Cycle · doi:10.4161/cc.4.3.1522 · Cited by 90
The tumorigenic potential and cell growth characteristics of p53-deficient cells are equivalent in the presence or absence of Mdm2
Jones, S. N., Sands, A., Hancock, A. R., Vogel, H. S., Donehower, L. A., Linke, S. P., Wahl, G. M., & Bradley, A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.14106 · Cited by 87
Self-citation
The Use of Genetic “Knockout” Mice in Behavioral Endocrinology Research
Nelson, R. J. (1997) · Hormones and Behavior · doi:10.1006/hbeh.1997.1381 · Cited by 87
Hdmx Recruitment into the Nucleus by Hdm2 Is Essential for Its Ability to Regulate p53 Stability and Transactivation
Migliorini, D., Danovi, D., Colombo, E., Carbone, R., Pelicci, P. G., & Marine, J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108795200 · Cited by 88
High levels of the p53 inhibitor MDM4 in head and neck squamous carcinomas
Valentin-Vega, Y. A., Barboza, J., Chau, G. P., El‐Naggar, A. K., & Lozano, G. (2007) · Human Pathology · doi:10.1016/j.humpath.2007.03.005 · Cited by 85
The RING domain of Mdm2 can inhibit cell proliferation.
Dang, J., Kuo, M.-L., Eischen, C. M., Stepanova, L., Sherr, C. J., & Roussel, M. F. (2002) · PubMed · Cited by 86
Targeted Deletion of the Tsg101 Gene Results in Cell Cycle Arrest at G1/S and p53-independent Cell Death
Krempler, A., Henry, M., Triplett, A. A., & Wagner, K. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207662200 · Cited by 86
Dysfunction of the MDM2/p53 axis is linked to premature aging
Lessel, D., Wu, D., Trujillo, C., Ramezani, T., Lessel, I., Alwasiyah, M. K., Saha, B., Hisama, F. M., Rading, K., Goebel, I., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92171 · Cited by 84
Uterine papillary serous carcinoma evolves via a p53-driven pathway
Moll, U. M., Chalas, E., Auguste, M., Meaney, D., & Chumas, J. C. (1996) · Human Pathology · doi:10.1016/s0046-8177(96)90340-8 · Cited by 86
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
“Knockout of mdm2 in mice causes embryonic lethality due to p53 activation, whereas knockout of both mdm2 and p53 completely rescues the lethality.(14,15) In addition, the lethality of the knockout mice of mdm4 (murine double minute 4), which encodes an Mdm2related p53-binding protein, can also be rescued by deletion o…”
Background
Uncovering Ubiquitin and Ubiquitin-like Signaling Networks
Vertegaal, A. C. O. (2011) · Chemical Reviews · doi:10.1021/cr200187e · Cited by 94
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Su, W., Fang, J., Cheng, F., Liu, C., Zhou, F., & Zhang, J. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211604110 · Cited by 87
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White, E. (1998) · Seminars in Virology · doi:10.1006/smvy.1998.0155 · Cited by 80
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Authors: Jones, S. N., Roe, A. E., Donehower, L. A., & Bradley, A.
Affiliations: Howard Hughes Medical Institute (US)
Baylor College of Medicine (US)
ORCID: Bradley, Allan
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 1995-11
Volume: 378
Issue: 6553
Pages: 206-208
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/378206a0
OpenAlex: W1993864973
Semantic Scholar: efc84bf5f5d1747443a3eb4555f9b5ede31b368f
Cited by: 1,280
References: 24
Citations by year: 2026: 9 · 2025: 17 · 2024: 30 · 2023: 31 · 2022: 28 · 2021: 35 · 2020: 41 · 2019: 28 · 2018: 31 · 2017: 38 · 2016: 54 · 2015: 34 · 2014: 59 · 2013: 30 · 2012: 60
FWCI: 14.50
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords: MDM2, p53, embryonic lethality, developmental regulation, tumor suppressor, sarcoma, leukemia
MeSH terms: Proto-Oncogene Mas, Animals, Base Sequence, Cell Cycle, Cell Line, Crosses, Genetic, Female, Embryonic and Fetal Development, Genes, Lethal, Molecular Sequence Data, Mutation, Nuclear Proteins, Proto-Oncogene Proteins, Tumor Suppressor Protein p53, 3T3 Cells, DNA Primers, Gene Targeting, Mice, Proto-Oncogene Proteins c-mdm2

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Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53

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