The p53 family in differentiation and tumorigenesis

Surfing the p53 network

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Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours

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p63 is essential for regenerative proliferation in limb, craniofacial and epithelial development

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Tumor spectrum analysis in p53-mutant mice

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p63 is a p53 homologue required for limb and epidermal morphogenesis

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Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome

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p73-deficient mice have neurological, pheromonal and inflammatory defects but lack spontaneous tumours

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p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression

Lin, T., Chao, C., Saito, S., Mazur, S. J., Murphy, M. E., Appella, E., & Xu, Y. (2004) · Nature Cell Biology · doi:10.1038/ncb1211 · Cited by 859 · see citing works

p53 isoforms can regulate p53 transcriptional activity

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p63 and p73 are required for p53-dependent apoptosis in response to DNA damage

Flores, E. R., Tsai, K. Y., Crowley, D. G., Sengupta, S., Yang, A., McKeon, F., & Jacks, T. (2002) · Nature · doi:10.1038/416560a · Cited by 801 · see citing works

p63 is the molecular switch for initiation of an epithelial stratification programPreprint

Koster, M. I., Kim, S., Mills, A. A., DeMayo, F. J., & Roop, D. R. (2004) · Genes & Development · doi:10.1101/gad.1165104 · Cited by 622 · see citing works

The biology of CML blast crisis

Calabretta, B., & Perrotti, D. (2004) · Blood · doi:10.1182/blood-2003-12-4111 · Cited by 591 · see citing works

A subset of p53-deficient embryos exhibit exencephaly

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Tumor predisposition in mice mutant for p63 and p73: Evidence for broader tumor suppressor functions for the p53 family

Flores, E. R., Sengupta, S., Miller, J. B., Newman, J. J., Bronson, R. T., Crowley, D. G., Yang, A., McKeon, F., & Jacks, T. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.02.019 · Cited by 499 · see citing works

p63 and p73: Roles in Development and Tumor Formation

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A subset of tumor-derived mutant forms of p53 down-regulate p63 and p73 through a direct interaction with the p53 core domain

Gaiddon, C., Lokshin, M., Ahn, J., Zhang, T., & Prives, C. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.5.1874-1887.2001 · Cited by 464 · see citing works

p63 mediates survival in squamous cell carcinoma by suppression of p73-dependent apoptosis

Rocco, J. W., Leong, C., Kuperwasser, N., DeYoung, M. P., & Ellisen, L. W. (2006) · Cancer Cell · doi:10.1016/j.ccr.2005.12.013 · Cited by 435 · see citing works

Links between Tumor Suppressors

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Unique association of p53 mutations with undifferentiated but not with differentiated carcinomas of the thyroid gland

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Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: cooperativity of Ink4a/ARF and Trp53 loss of functionPreprint

Keller, C., Arenkiel, B. R., Coffin, C. M., Bardeesy, N. M., DePinho, R. A., & Capecchi, M. R. (2004) · Genes & Development · doi:10.1101/gad.1244004 · Cited by 304 · see citing works

Differential roles of p63 isoforms in epidermal development: selective genetic complementation in p63 null mice

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Induction of Neuronal Differentiation by p73 in a Neuroblastoma Cell Line

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Expression of ΔNp73 is a molecular marker for adverse outcome in neuroblastoma patients

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Mice with reduced levels of p53 protein exhibit the testicular giant-cell degenerative syndrome.

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Involvement of p53 in cell differentiation and development

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Role of p73 in malignancy: tumor suppressor or oncogene?

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Small-Molecule MDM2 Antagonists as a New Therapy Concept for Neuroblastoma

Maerken, T. V., Speleman, F., Vermeulen, J., Lambertz, I., Clercq, S. D., Smet, E. D., Yigit, N., Coppens, V., Philippé, J., Paepe, A. D., et al. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0792 · Cited by 154 · see citing works

Childhood solid tumours: a developmental disorder

Scotting, P. J., Walker, D. A., & Perilongo, G. (2005) · Nature reviews. Cancer · doi:10.1038/nrc1633 · Cited by 152 · see citing works

P53 Regulates Myogenesis by Triggering the Differentiation Activity of Prb

Porrello, A., Cerone, M. A., Coen, S., Gurtner, A., Fontemaggi, G., Cimino, L., Piaggio, G., Sacchi, A., & Soddu, S. (2000) · The Journal of Cell Biology · doi:10.1083/jcb.151.6.1295 · Cited by 121 · see citing works

p53 family members in myogenic differentiation and rhabdomyosarcoma development

Çam, H., Griesmann, H., Beitzinger, M., Hofmann, L., Beinoravičiūtė-Kellner, R., Sauer, M., Hüttinger-Kirchhof, N., Oswald, C., Friedl, P., Gattenlöhner, S., et al. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.08.024 · Cited by 109 · see citing works

p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors

Keyes, W. M., Vogel, H. S., Koster, M. I., Guo, X., Qi, Y., Petherbridge, K. M., Roop, D. R., Bradley, A., & Mills, A. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602477103 · Cited by 88 · see citing works

Comprehensive genomics linking between neural development and cancer: neuroblastoma as a model.

Nakagawara, A., & Ohira, M. (2004) · Cancer Letters · doi:10.1016/s0304-3835(03)00457-9 · Cited by 81 · see citing works

Rhabdomyosarcoma development in mice lacking Trp53 and Fos

Fleischmann, A., Jochum, W., Eferl, R., Witowsky, J. A., & Wagner, E. F. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00280-0 · Cited by 71 · see citing works

Development of rhabdomyosarcoma in HER-2/neu transgenic p53 mutant mice.

Nanni, P., Nicoletti, G., Giovanni, C. D., Croci, S., Astolfi, A., Landuzzi, L., Carlo, E. D., Iezzi, M., Musiani, P., & Lollini, P. (2003) · PubMed · Cited by 69 · see citing works

δEF1 repressor controls selectively p53 family members during differentiation

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Spatiotemporal Switch from ΔNp73 to TAp73 Isoforms during Nephrogenesis

Saifudeen, Z. R., Diavolitsis, V. M., Stefkova, J., Dipp, S., Fan, H., & El-Dahr, S. S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414575200 · Cited by 29 · see citing works

The p53 family inhibitor ΔNp73 interferes with multiple developmental programs

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Deregulated expression of ΔNp73α causes early embryonic lethality

Erster, S. H., Palacios, G. F., Rosenquist, T. A., Chang, C. H. S., & Moll, U. M. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401743 · Cited by 10 · see citing works

The first 30 years of p53: growing ever more complex.

Levine, A. J., & Oren, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2723 · Cited by 1,967 · see citing works

MicroRNA-21 Targets a Network of Key Tumor-Suppressive Pathways in Glioblastoma Cells

Papagiannakopoulos, T., Shapiro, A., & Kosik, K. S. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-1305 · Cited by 705 · see citing works

p53 polymorphisms: cancer implications

Whibley, C., Pharoah, P. D. P., & Hollstein, M. C. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2584 · Cited by 667 · see citing works

Biological response of cancer cells to radiation treatment

Baskar, R., Dai, J., Nei, W. L., Yeo, R., & Yeoh, K. (2014) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2014.00024 · Cited by 638 · see citing works

Strategies for optimizing the response of cancer and normal tissues to radiation

Moding, E. J., Kastan, M. B., & Kirsch, D. G. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4003 · Cited by 461 · see citing works

Small-Molecule Inhibitors of the MDM2–p53 Protein–Protein Interaction (MDM2 Inhibitors) in Clinical Trials for Cancer Treatment

Zhao, Y., Aguilar, A., Bernard, D., & Wang, S. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm501092z · Cited by 462 · see citing works

TAp73 knockout shows genomic instability with infertility and tumor suppressor functionsPreprint

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The role of mutant p53 in human cancer

Goh, A. M., Coffill, C. R., & Lane, D. P. (2010) · The Journal of Pathology · doi:10.1002/path.2784 · Cited by 398 · see citing works

Shaping Genetic Alterations in Human Cancer: The p53 Mutation Paradigm

Soussi, T., & Wiman, K. G. (2007) · Cancer Cell · doi:10.1016/j.ccr.2007.10.001 · Cited by 366 · see citing works

GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability

Hu, W. L., Jin, L., Xu, A., Wang, Y. F., Thorne, R. F., Zhang, X. D., & Wu, M. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0066-7 · Cited by 348 · see citing works

Discovery of MD-224 as a First-in-Class, Highly Potent, and Efficacious Proteolysis Targeting Chimera Murine Double Minute 2 Degrader Capable of Achieving Complete and Durable Tumor Regression

Li, Y., Yang, J., Aguilar, A., McEachern, D., Przybranowski, S., Liu, L., Yang, C.-Y., Wang, M., Han, X., & Wang, S. (2019) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00909 · Cited by 312 · see citing works

Targeting the MDM2–p53 Protein–Protein Interaction for New Cancer Therapy: Progress and Challenges

Wang, S., Zhao, Y., Aguilar, A., Bernard, D., & Yang, C.-Y. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026245 · Cited by 300 · see citing works

Trim24 targets endogenous p53 for degradation

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Nucleolar stress with and without p53

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The p53 family: guardians of maternal reproduction

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Cellular signaling perturbation by natural products

Sarkar, F. H., Li, Y., Wang, Z. P., & Kong, D. (2009) · Cellular Signalling · doi:10.1016/j.cellsig.2009.03.009 · Cited by 248 · see citing works

p53 and its isoforms in cancer

Bourdon, J. (2007) · British Journal of Cancer · doi:10.1038/sj.bjc.6603886 · Cited by 243 · see citing works

Molecular mechanisms of cervical carcinogenesis by high‐risk human papillomaviruses: novel functions of E6 and E7 oncoproteins

Yugawa, T., & Kiyono, T. (2009) · Reviews in Medical Virology · doi:10.1002/rmv.605 · Cited by 236 · see citing works

DNA Mismatch Repair Gene Polymorphisms Affect Survival in Pancreatic Cancer

Dong, X., Li, Y., Hess, K. R., Abbruzzese, J. L., & Li, D. (2011) · The Oncologist · doi:10.1634/theoncologist.2010-0127 · Cited by 216 · see citing works

Flavonoids as Protein Kinase Inhibitors for Cancer Chemoprevention: Direct Binding and Molecular Modeling

Hou, D., & Kumamoto, T. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2816 · Cited by 212 · see citing works

Revealing Global Regulatory Perturbations across Human Cancers

Goodarzi, H., Elemento, O., & Tavazoie, S. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.11.016 · Cited by 201 · see citing works

20 years studying p53 functions in genetically engineered mice

Donehower, L. A., & Lozano, G. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2731 · Cited by 193 · see citing works

Crosstalk of Notch with p53 and p63 in cancer growth control

Dotto, G. P. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2675 · Cited by 189 · see citing works

PAX3–FOXO1 fusion gene in rhabdomyosarcoma

Linardic, C. M. (2008) · Cancer Letters · doi:10.1016/j.canlet.2008.03.035 · Cited by 176 · see citing works

Circadian Clock, Cancer, and Chemotherapy

Sancar, A., Lindsey-Boltz, L. A., Gaddameedhi, S., Selby, C. P., Ye, R., Chiou, Y.-Y., Kemp, M. G., Hu, J., Lee, J. H., & Ozturk, N. (2015) · Biochemistry · doi:10.1021/bi5007354 · Cited by 170 · see citing works

One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy

Shuvalov, O., Petukhov, A., Daks, A., Fedorova, O., Vasileva, E., & Barlev, N. A. (2017) · Oncotarget · doi:10.18632/oncotarget.15053 · Cited by 168 · see citing works

p53 Plays a Role in Mesenchymal Differentiation Programs, in a Cell Fate Dependent Manner

Molchadsky, A., Shats, I., Goldfinger, N., Pevsner‐Fischer, M., Olson, M., Rinon, A., Tzahor, E., Lozano, G., Zipori, D., Sarig, R., et al. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003707 · Cited by 158 · see citing works

p53 is balancing development, differentiation and de-differentiation to assure cancer prevention

Molchadsky, A., Rivlin, N., Brosh, R., Rotter, V., & Sarig, R. (2010) · Carcinogenesis · doi:10.1093/carcin/bgq101 · Cited by 156 · see citing works

p53 downregulates Down syndrome‐associated DYRK1A through miR‐1246

Zhang, Y., Liao, J., Zeng, S. X., & Lu, H. (2011) · EMBO Reports · doi:10.1038/embor.2011.98 · Cited by 146 · see citing works

p53 and stem cells: new developments and new concerns

Zhao, T., & Xu, Y. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2009.12.004 · Cited by 141 · see citing works

Next-generation sequencing of acute myeloid leukemia identifies the significance of TP53, U2AF1, ASXL1, and TET2 mutations

Ohgami, R. S., Ma, L., Merker, J. D., Gotlib, J. R., Schrijver, I., Zehnder, J. L., & Arber, D. A. (2014) · Modern Pathology · doi:10.1038/modpathol.2014.160 · Cited by 139 · see citing works

Cell death in the skin

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Ion beam radiobiology and cancer: Time to update ourselves

Fokas, E., Kraft, G., An, H., & Engenhart‐Cabillic, R. (2009) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2009.07.005 · Cited by 134 · see citing works

Back to basics: how natural products can provide the basis for new therapeutics

Deorukhkar, A., Krishnan, S., Sethi, G., & Aggarwal, B. B. (2007) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.16.11.1753 · Cited by 130 · see citing works

RRM2 Regulates Bcl-2 in Head and Neck and Lung Cancers: A Potential Target for Cancer Therapy

Rahman, M. A., Amin, A. R. M. R., Wang, D., Koenig, L., Nannapaneni, S., Chen, Z., Wang, Z., Sica, G., Deng, X., Chen, Z., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-13-0073 · Cited by 127 · see citing works

Repeated PM2.5 exposure inhibits BEAS-2B cell P53 expression through ROS-Akt-DNMT3B pathway-mediated promoter hypermethylation

Zhou, W. J., Tian, D., He, J., Wang, Y., Zhang, L., Cui, L., Li, J., Zhang, L., Li, L., Shu, Y., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.7842 · Cited by 123 · see citing works

ΔNp63 Versatilely Regulates a Broad NF-κB Gene Program and Promotes Squamous Epithelial Proliferation, Migration, and Inflammation

Yang, X., Lü, H., Yan, B., Romano, R.-A., Bian, Y., Friedman, J., Duggal, P., Allen, C. T., Chuang, R. J., Ehsanian, R., et al. (2011) · Cancer Research · doi:10.1158/0008-5472.can-10-3445 · Cited by 122 · see citing works

p53: emerging roles in stem cells, development and beyond

Jain, A. K., & Barton, M. C. (2018) · Development · doi:10.1242/dev.158360 · Cited by 121 · see citing works

Regulation of p53 is critical for vertebrate limb regeneration

Yun, M. H., Gates, P. B., & Brockes, J. P. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1310519110 · Cited by 112 · see citing works

DNA Binding Cooperativity of p53 Modulates the Decision between Cell-Cycle Arrest and Apoptosis

Schlereth, K., Beinoraviciute-Kellner, R., Zeitlinger, M. K., Bretz, A. C., Sauer, M., Charles, J. P., Vogiatzi, F., Leich, E., Samans, B., Eilers, M., et al. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.02.037 · Cited by 113 · see citing works

Intermolecular Interactions of Sprouty Proteins and Their Implications in Development and Disease

Edwin, F., Anderson, K. M., Ying, C., & Patel, T. B. (2009) · Molecular Pharmacology · doi:10.1124/mol.109.055848 · Cited by 114 · see citing works

p53 coordinates cranial neural crest cell growth and epithelial-mesenchymal transition/delamination processes

Rinon, A., Molchadsky, A., Nathan, E., Yovel, G., Rotter, V., Sarig, R., & Tzahor, E. (2011) · Development · doi:10.1242/dev.053645 · Cited by 111 · see citing works

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 105 · see citing works

Small-molecule MDM2 inhibitors in clinical trials for cancer therapy

Wang, S., & Chen, F. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114334 · Cited by 102 · see citing works

Evidence for a biphasic apoptotic pathway induced by melatonin in MCF‐7 breast cancer cells

Cucina, A., Proietti, S., D’Anselmi, F., Coluccia, P., Dinicola, S., Frati, L., & Bizzarri, M. (2009) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2008.00645.x · Cited by 101 · see citing works

Chemotherapy‐induced apoptosis in hepatocellular carcinoma involves the p53 family and is mediated via the extrinsic and the intrinsic pathway

Seitz, S., Schleithoff, E. S., Koch, A., Schuster, A., Teufel, A., Staib, F., Stremmel, W., Melino, G., Krammer, P. H., Schilling, T., et al. (2009) · International Journal of Cancer · doi:10.1002/ijc.24861 · Cited by 93 · see citing works

Genistein Enhances the Radiosensitivity of Breast Cancer Cells via G2/M Cell Cycle Arrest and Apoptosis

Liu, X., Sun, C., Jin, X., Li, P., Ye, F., Zhao, T., Gong, L., & Li, Q. (2013) · Molecules · doi:10.3390/molecules181113200 · Cited by 93 · see citing works

Elucidating the cancer-specific genetic alteration spectrum of glioblastoma derived cell lines from whole exome and RNA sequencing

Patil, V. S., Pal, J., & Somasundaram, K. (2015) · Oncotarget · doi:10.18632/oncotarget.6171 · Cited by 91 · see citing works

In vivo analysis of p53 tumor suppressor function using genetically engineered mouse models

Brož, D. K., & Attardi, L. D. (2010) · Carcinogenesis · doi:10.1093/carcin/bgp331 · Cited by 89 · see citing works

Characterization of the p53 Cistrome – DNA Binding Cooperativity Dissects p53's Tumor Suppressor Functions

Schlereth, K., Heyl, C., Krampitz, A.-M., Mernberger, M., Finkernagel, F., Scharfe, M., Jarek, M., Leich, E., Rosenwald, A., & Stiewe, T. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003726 · Cited by 87 · see citing works

Molecular Mechanisms and Pathways as Targets for Cancer Prevention and Progression with Dietary Compounds

Nosrati, N., Bakovic, M., & Paliyath, G. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102050 · Cited by 88 · see citing works

NFκB/p53 crosstalk—a promising new therapeutic target

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Regulation of p53 family members by the ubiquitin-like SUMO system

Stehmeier, P., & Muller, S. (2009) · DNA repair · doi:10.1016/j.dnarep.2009.01.002 · Cited by 83 · see citing works

Dual roles of Drosophila p53 in cell death and cell differentiation

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MicroRNA-21 silencing enhances the cytotoxic effect of the antiangiogenic drug sunitinib in glioblastoma

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