The DOI matches its Crossref record; 30 of the 31 references it cites were found in a registry or an index.
HDM2 antagonist Nutlin-3 disrupts p73-HDM2 binding and enhances p73 function
Abstract
Nutlin-3, a small molecule inhibitor, activates p53 by disrupting p53-HDM2 association. In this study, we found that Nutlin-3 suppressed cell growth and induced apoptosis in the absence of wild-type p53, suggesting a p53-independent mechanism for Nutlin-3-induced cell death. Like p53, its homolog p73 transactivates proapoptotic genes and induces cell death. Since HDM2, a key negative regulator of p53, also binds to and inhibits p73, we asked whether p73 could mediate Nutlin-3-induced apoptosis. We demonstrate that Nutlin-3 inhibits endogenous binding between the proapoptotic p73 isoform TAp73alpha and HDM2 in p53-null cells. Dissociation of p73 and HDM2 leads to increased p73 transcriptional activity with upregulation of p73 target genes noxa, puma and p21, as well as enhanced apoptosis. p73 knockdown by siRNA results in rescue of Nutlin-3-treated cells, indicating that Nutlin-3-induced apoptosis is, at least in part, p73 dependent. In addition, Nutlin-3 treatment increases TAp73alpha protein levels with prolongation of p73 half-life. These results provide the first evidence that Nutlin-3 disrupts endogenous p73-HDM2 interaction and enhances the stability and proapoptotic activities of p73 and thus, provides a rationale for the use of Nutlin-3 in the large number of human tumors in which p53 is inactivated.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“The MDM2 protein–protein interaction (PPI) inhibitor nutlin3a binds to the N-terminal hydrophobic pocket of MDM2 and blocks interaction of MDM2 with not only p53 but also a number of other key signal transducers, including p73α, E2F1, Rb, and HIF-1α”
From Combination therapy in a xenograft model of glioblastoma: Enhancement of the antitumor activity of temozolomide by an MDM2 antagonist (2017) · cites this paper as [22]
In the citing paper
“information on dosing regimens that build upon front-line chemotherapy for GBM is lacking.19,21,22,34,43,45”
From Combination therapy in a xenograft model of glioblastoma: Enhancement of the antitumor activity of temozolomide by an MDM2 antagonist (2017) · cites this paper as [22]
In the citing paper
“Nutlin-3a also inhibits the binding of the p73 isoform p73α, as well as E2F1 and hypoxia inducible factor 1α (Hif-1α), to the N-terminal hydrophobic pocket of Mdm2 (11–13).”
From Potentiation of carboplatin-mediated DNA damage by the Mdm2 modulator Nutlin-3a in a humanized orthotopic breast-to-lung metastatic model (2015) · cites this paper as [12]
In the citing paper
“Lau and colleagues showed that when cells were treated with Nutlin-3a, the binding of p73α to Mdm2 was inhibited, leading to p73α-mediated induction of pro-apoptotic downstream targets and increased apoptosis in cells lacking wild-type p53 (12).”
From Potentiation of carboplatin-mediated DNA damage by the Mdm2 modulator Nutlin-3a in a humanized orthotopic breast-to-lung metastatic model (2015) · cites this paper as [12]
In the citing paper
“While p53 and p73α can both interact with Mdm2 in the same N-terminal hydrophobic pocket (12), Mdm2 does not ubiquitinate p73α (44–46).”
From Potentiation of carboplatin-mediated DNA damage by the Mdm2 modulator Nutlin-3a in a humanized orthotopic breast-to-lung metastatic model (2015) · cites this paper as [12]
In the citing paper
“These data are consistent with previous reports indicating that p73α can directly bind to the Mdm2 promoter and increase Mdm2 gene expression (12, 47).”
From Potentiation of carboplatin-mediated DNA damage by the Mdm2 modulator Nutlin-3a in a humanized orthotopic breast-to-lung metastatic model (2015) · cites this paper as [12]
In the citing paper
“Blockade of the binding of Mdm2 to p73α by Nutlin-3a increases the pool of p73α available to transcriptionally activate pro-apoptotic gene expression and promote apoptosis in mutant p53 and p53 null cells (12).”
From Potentiation of carboplatin-mediated DNA damage by the Mdm2 modulator Nutlin-3a in a humanized orthotopic breast-to-lung metastatic model (2015) · cites this paper as [12]
Citations
Cites
In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2
Vassilev, L. T., Vu, B. T., Graves, B., Carvajal, D., Podlaski, F., Filipovic, Z., Kong, N., Kammlott, U., Lukacs, C., Klein, C., et al. (2004) · Science · doi:10.1126/science.1092472 · Cited by 4,661
Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain
Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., & Pavletich, N. P. (1996) · Science · doi:10.1126/science.274.5289.948 · Cited by 2,206
Role for the p53 homologue p73 in E2F-1-induced apoptosis
Irwin, M. S., Marín, M. C., Phillips, A. C., Seelan, R. S., Smith, D. I., Liu, W., Flores, E. R., Tsai, K. Y., Jacks, T., Vousden, K. H., et al. (2000) · Nature · doi:10.1038/35036614 · Cited by 710
Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: implications for therapy
Tovar, C., Rosinski, J., Filipovic, Z., Higgins, B., Kolinsky, K., Hilton, H., Zhao, X., Vu, B. T., Qing, W., Packman, K., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507493103 · Cited by 708
Inactivation of the p53 pathway in retinoblastoma
Laurie, N. A., Donovan, S. L., Shih, C.-S., Zhang, J., Mills, N., Fuller, C., Teunisse, A., Lam, S., Ramos, Y., Mohan, A., et al. (2006) · Nature · doi:10.1038/nature05194 · Cited by 595
AIS is an oncogene amplified in squamous cell carcinoma
Hibi, K., Trink, B., Patturajan, M., Westra, W. H., Caballero, O. L., Hill, D. E., Ratovitski, E. A., Jen, J., & Sidransky, D. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.10.5462 · Cited by 464
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
Chemosensitivity linked to p73 function
Irwin, M. S., Kondo, K., Marín, M. C., Cheng, L. S., Hahn, W. C., & Kaelin, W. G. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00078-3 · Cited by 406
Iwakuma, T., & Lozano, G. (2003) · PubMed · Cited by 390
MDM2 suppresses p73 function without promoting p73 degradation
Zeng, X., Chen, L., Jost, C. A., Maya, R., Keller, D., Wang, X., Kaelin, W. G., Oren, M., Chen, J., & Lu, H. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.5.3257 · Cited by 334
Cited by
Sorted by citations
The role of p53 in cancer drug resistance and targeted chemotherapy
Hientz, K., Mohr, A., Bhakta-Guha, D., & Efferth, T. (2016) · Oncotarget · doi:10.18632/oncotarget.13475 · Cited by 612
Dutt, S., Narla, A., Lin, K. I., Mullally, A., Abayasekara, N., Megerdichian, C., Wilson, F. H., Currie, T., Khanna‐Gupta, A., Berliner, N., et al. (2010) · Blood · doi:10.1182/blood-2010-07-295238 · Cited by 410
Translating p53 into the clinic
Cheok, C. F., Verma, C. S., Baselga, J., & Lane, D. P. (2011) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2010.174 · Cited by 381
Targeting the MDM2-p53 Interaction for Cancer Therapy
Shangary, S. K., & Wang, S. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-07-5136 · Cited by 372
p53 Family and Cellular Stress Responses in Cancer
Pflaum, J., Schlosser, S., & ller, M. M. ⁄. (2014) · Frontiers in Oncology · doi:10.3389/fonc.2014.00285 · Cited by 309
Noxa: at the tip of the balance between life and death
Ploner, C., Kofler, R., & Villunger, A. (2008) · Oncogene · doi:10.1038/onc.2009.46 · Cited by 291
Tisato, V., Voltan, R., Gonelli, A., Secchiero, P., & Zauli, G. (2017) · Journal of Hematology & Oncology · doi:10.1186/s13045-017-0500-5 · Cited by 259
Targeting p53 for Novel Anticancer Therapy
Wang, Z., & Sun, Y. (2010) · Translational Oncology · doi:10.1593/tlo.09250 · Cited by 256
p53-based Cancer TherapyPreprint
Lane, D. P., Cheok, C. F., & Laı́n, S. (2010) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001222 · Cited by 251
Marti, P., Stein, C., Blumer, T., Abraham, Y., Dill, M. T., Pikiolek, M., Orsini, V., Jurisic, G., Megel, P., Makowska, Z., et al. (2015) · Hepatology · doi:10.1002/hep.27992 · Cited by 232
Tumour suppression by p53: the importance of apoptosis and cellular senescence
Zuckerman, V., Wolyniec, K., Sionov, R. V., Haupt, S., & Haupt, Y. (2009) · The Journal of Pathology · doi:10.1002/path.2584 · Cited by 222
Targeting the p53 signaling pathway in cancer therapy – the promises, challenges and perils
Stegh, A. H. (2012) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2011.643299 · Cited by 198
Current developments of targeting the p53 signaling pathway for cancer treatment
Huang, J. L. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107720 · Cited by 157
Pharmacologic Activation of p53 by Small-Molecule MDM2 Antagonists
Shen, H., & Maki, C. G. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211795222603 · Cited by 148
Rufini, A., Agostini, M., Grespi, F., Tomasini, R., Sayan, B. S., Niklison-Chirou, M. V., Conforti, F., Velletri, T., Mastino, A., Mak, T. W., et al. (2011) · Genes & Cancer · doi:10.1177/1947601911408890 · Cited by 151
Effect of low doses of actinomycin D on neuroblastoma cell lines
Cortes, C. L., Veiga, S. R., Almacellas, E., Hernández‐Losa, J., Ferreres, J. C., Kozma, S. C., Ambrosio, S., Thomas, G., & Tauler, A. (2016) · Molecular Cancer · doi:10.1186/s12943-015-0489-8 · Cited by 132
The roles and regulation of MDM2 and MDMX: it is not just about p53Preprint
Klein, A. M., de Queiroz, R. M., Venkatesh, D., & Prives, C. L. (2021) · Genes & Development · doi:10.1101/gad.347872.120 · Cited by 138
Thomasová, D., Mulay, S. R., Bruns, H., & Anders, H. (2012) · Neoplasia · doi:10.1593/neo.121534 · Cited by 126
Novel targeted therapeutics: inhibitors of MDM2, ALK and PARP
Yuan, Y., Liao, Y.-M., Hsueh, C.-T., & Mirshahidi, H. (2011) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-4-16 · Cited by 120
Targeting p53 by small molecules in hematological malignancies
Saha, M. N., Qiu, L., & Chang, H. H. (2013) · Journal of Hematology & Oncology · doi:10.1186/1756-8722-6-23 · Cited by 112
Das, M., Duan, W., & Sahoo, S. K. (2014) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2014.09.002 · Cited by 112
Targeting the p53-MDM2 pathway for neuroblastoma therapy: Rays of hope
Zafar, A., Wang, W., Liu, G., Xian, W., McKeon, F., Zhou, J., & Zhang, R. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.09.023 · Cited by 108
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
Ray, R. M., Bhattacharya, S., & Johnson, L. R. (2010) · APOPTOSIS · doi:10.1007/s10495-010-0538-0 · Cited by 100
Preeclampsia Is Associated with Alterations in the p53-Pathway in Villous Trophoblast
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
PRIMA-1Met/APR-246 Displays High Antitumor Activity in Multiple Myeloma By Induction of p73 and Noxa
Saha, M. N., Jiang, H., Yang, Y., Reece, D. E., & Chang, H. (2013) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-12-1166 · Cited by 99
Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy
Song, B., Yang, P., & Zhang, S. (2024) · 癌症：英文版 · doi:10.1002/cac2.12520 · Cited by 103
Roh, J., Kang, S. K., Minn, I., Califano, J. A., Sidransky, D., & Koch, W. M. (2010) · Oral Oncology · doi:10.1016/j.oraloncology.2010.10.011 · Cited by 92
CRISPR-Cas9–based target validation for p53-reactivating model compounds
Wanzel, M., Vischedyk, J. B., Gittler, M. P., Gremke, N., Seiz, J. R., Hefter, M., Noack, M., Savai, R., Mernberger, M., Charles, J. P., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1965 · Cited by 87
BH3-Only Proteins Noxa and Puma Are Key Regulators of Induced Apoptosis
Roufayel, R., Younes, K., Al-Sabi, A., & Murshid, N. (2022) · Life · doi:10.3390/life12020256 · Cited by 98
Kitagawa, M., Aonuma, M., Lee, S. H., Fukutake, S., & McCormick, F. P. (2008) · Oncogene · doi:10.1038/onc.2008.164 · Cited by 89
Arnhold, V., Schmelz, K., Proba, J., Winkler, A., Wünschel, J., Toedling, J., Deubzer, H. E., Künkele, A., Eggert, A., Schulte, J. H., et al. (2018) · Oncotarget · doi:10.18632/oncotarget.23409 · Cited by 85
Tabe, Y., Sebasigari, D., Jin, L., Rudelius, M., Davies-Hill, T., Miyake, K., Miida, T., Pittaluga, S., & Raffeld, M. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0399 · Cited by 83
McCormack, E., Haaland, I., Venås, G., Forthun, R. B., Huseby, S., Gausdal, G., Knappskog, S., Micklem, D., Lorens, J. B., Bruserud, Ø., et al. (2011) · Leukemia · doi:10.1038/leu.2011.315 · Cited by 83
Targeting the Ubiquitin-Proteasome System for Cancer Therapeutics by Small-Molecule Inhibitors
LaPlante, G., & Zhang, W. (2021) · Cancers · doi:10.3390/cancers13123079 · Cited by 88
Rastogi, S., Rizwani, W., Joshi, B., Kunigal, S., & Chellappan, S. (2011) · Cell Death and Differentiation · doi:10.1038/cdd.2011.93 · Cited by 82
MDM2 antagonist Nutlin-3a potentiates antitumour activity of cytotoxic drugs in sarcoma cell lines
Ohnstad, H. O., Paulsen, E. B., Noordhuis, P., Berg, M., Lothe, R. A., Vassilev, L. T., & Myklebost, O. (2011) · BMC Cancer · doi:10.1186/1471-2407-11-211 · Cited by 80
Lakoma, A., Barbieri, E., Agarwal, S., Jackson, J. R., Chen, Z., Kim, Y., McVay, M. C., Shohet, J. M., & Kim, E. S. (2015) · Cell Death Discovery · doi:10.1038/cddiscovery.2015.26 · Cited by 77
Deben, C., Wouters, A., de Beeck, K. O., van Den Bossche, J., Jacobs, J., Zwaenepoel, K., Peeters, M., Van Meerbeeck, J., Lardon, F., Rolfo, C., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.4433 · Cited by 73
Polo-Like Kinase 1 Depletion Induces DNA Damage in Early S Prior to Caspase Activation
Yim, H., & Erikson, R. L. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.01277-08 · Cited by 73
Targeting the MDM2-p53 protein–protein interaction for new cancer therapeutics
Wang, S., Zhao, Y., Bernard, D., Aguilar, A., & Kumar, S. (2012) · Topics in Medicinal Chemistry · doi:10.1007/978-3-642-28965-1_2 · Cited by 72
Dithiocarbamate-inspired side chain stapling chemistry for peptide drug design
Li, X., Tolbert, W. D., Hu, H., Gohain, N., Zou, Y., Niu, F., He, W., Yuan, W., Su, J., Pazgier, M., et al. (2018) · Chemical Science · doi:10.1039/c8sc03275k · Cited by 73
Zhang, L., McGraw, K. L., Sallman, D. A., & List, A. F. (2016) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.1080/10428194.2016.1266625 · Cited by 67
Azmi, A. S., Aboukameel, A., Banerjee, S., Wang, Z., Mohammad, M., Wu, J., Wang, S., Yang, D., Philip, P. A., Sarkar, F. H., et al. (2010) · European Journal of Cancer · doi:10.1016/j.ejca.2010.01.015 · Cited by 67
Drakos, E., Singh, R. R., Rassidakis, G. Z., Schlette, E. J., Li, J., Claret, F. X., Ford, R. J., Vega, F., & Medeiros, L. J. (2011) · Leukemia · doi:10.1038/leu.2011.28 · Cited by 67
Peirce (2009) · International Journal of Oncology · doi:10.3892/ijo_00000267 · Cited by 67
Hároníková, L., Bonczek, O., Zatloukalová, P., Kokas, F. Z., Kucerikova, M., Coates, P. J., Fåhræus, R., & Vojtěšek, B. (2021) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-021-00293-6 · Cited by 72
Murine double minute 2: p53-independent roads lead to genome instability or death
Bouska, A. C., & Eischen, C. M. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.02.006 · Cited by 68
New strategies in soft tissue sarcoma treatment
Ceruso, M. S., El-Ghazzi, N., & Italiano, A. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01580-3 · Cited by 71
Targeting the MDM2-p53 pathway in dedifferentiated liposarcoma
Traweek, R. S., Cope, B. M., Roland, C. L., Keung, E. Z.-Y., Nassif, E. F., & Erstad, D. J. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1006959 · Cited by 64
Zheng, T., Yin, D., Lu, Z., Wang, J., Li, Y., Chen, X., Liang, Y., Song, X., Qi, S., Sun, B., et al. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-133 · Cited by 60
Neuroblastoma: oncogenic mechanisms and therapeutic exploitation of necroptosis
Nicolai, S., Pieraccioli, M., Peschiaroli, A., Melino, G., & Raschellà, G. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.354 · Cited by 62
Mdm2 Is Required for Survival and Growth of p53-Deficient Cancer Cells
Feeley, K. P., Adams, C. M., Mitra, R., & Eischen, C. M. (2017) · Cancer Research · doi:10.1158/0008-5472.can-17-0809 · Cited by 57
p53 stabilization induces apoptosis in chronic myeloid leukemia blast crisis cells
Peterson, L. F., Mitrikeska, E., Giannola, D. M., Lui, Y., Sun, H., Bixby, D. L., Malek, S. N., Donato, N. J., Wang, S., & Talpaz, M. (2011) · Leukemia · doi:10.1038/leu.2011.7 · Cited by 55
Mdm2 and MdmX as Regulators of Gene Expression
Biderman, L., Manley, J. L., & Prives, C. L. (2012) · Genes & Cancer · doi:10.1177/1947601912455331 · Cited by 58
p53 Modulation as a Therapeutic Strategy in Gastrointestinal Stromal Tumors
Henze, J., Mühlenberg, T., Simon, S., Grabellus, F., Rubin, B. P., Taeger, G., Schüler, M., Treckmann, J. W., Dêbiec‐Rychter, M., Taguchi, T., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037776 · Cited by 54
The p53 Family Protein p73 Provides New Insights into Cancer Chemosensitivity and Targeting
Lunghi, P., Costanzo, A., Mazzera, L., Rizzoli, V., Levrero, M., & Bonati, A. (2009) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-09-1229 · Cited by 54
Therapeutic prospects for p73 and p63: Rising from the shadow of p53
Vilgelm, A. E., El-Rifai, W. M., & Zaika, A. I. (2008) · Drug Resistance Updates · doi:10.1016/j.drup.2008.08.001 · Cited by 53
Nutlin-3 enhances the bortezomib sensitivity of p53-defective cancer cells by inducing paraptosis
Lee, D. M., Kim, I. Y., Seo, M. J., Kwon, M. R., & Choi, K. S. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.112 · Cited by 52
Targeting the ubiquitin–proteasome system to activate wild-type p53 for cancer therapy
Allende-Vega, N., & Saville, M. K. (2009) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2009.10.004 · Cited by 51
Zheng, T., Wang, J., Song, X., Meng, X., Pan, S., Jiang, H., & Liu, L. (2010) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-010-0817-8 · Cited by 51
MDM2 Inhibitor Nutlin-3a Induces Apoptosis and Senescence in Cutaneous T-Cell Lymphoma: Role of p53
Manfé, V., Biskup, E., Johansen, P., Kamstrup, M. R., Krejsgaard, T., Morling, N., Wulf, H. C., & Gniadecki, R. (2012) · Journal of Investigative Dermatology · doi:10.1038/jid.2012.10 · Cited by 51
Wang, H., Cai, S., Bailey, B. J., Reza Saadatzadeh, M., Ding, J., Tonsing-Carter, E., Georgiadis, T. M., Zachary Gunter, T., Long, E. C., Minto, R. E., et al. (2017) · Journal of Neurosurgery · doi:10.3171/2016.1.jns152513 · Cited by 49
MDM2, MDMX, and p73 regulate cell-cycle progression in the absence of wild-type p53
Klein, A. M., Biderman, L., Tong, D., Alaghebandan, B., Plumber, S. A., Mueller, H. S., van Vlimmeren, A. E., Katz, C., & Prives, C. L. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2102420118 · Cited by 48
Lai, C.-Y., Tsai, A.-C., Chen, M.-C., Chang, L.-H., Sun, H., Chang, Y.-L., Chen, C.-C., Teng, C., & Pan, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042192 · Cited by 51
Nutlins and Ionizing Radiation in Cancer Therapy
Impicciatore, G. G., Sancilio, S., Miscia, S., & Pietro, R. D. (2010) · Current Pharmaceutical Design · doi:10.2174/138161210791033932 · Cited by 50
Pharmacologic activation of wild-type p53 by nutlin therapy in childhood cancer
Maerken, T. V., Rihani, A., Goethem, A. V., Paepe, A. D., Speleman, F., & Vandesompele, J. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.11.002 · Cited by 47
MDM2-p53 Interaction in Paediatric Solid Tumours: Preclinical Rationale, Biomarkers and Resistance
Barone, G., Tweddle, D. A., Shohet, J. M., Chesler, L., Moreno, L., Pearson, A. D. J., & Maerken, T. V. (2014) · Current Drug Targets · doi:10.2174/13894501113149990194 · Cited by 45
Das, R., Bhattacharya, K., Sarkar, S., Samanta, S. K., Pal, B. C., & Mandal, C. (2013) · APOPTOSIS · doi:10.1007/s10495-013-0907-6 · Cited by 45
RetractedLin, H., Wang, L., Liu, Z., Long, K., Kong, M., Ye, D., Chen, X., Wang, K., Wu, K. K., Fan, M., et al. (2022) · Advanced Science · doi:10.1002/advs.202200742 · Cited by 43
Drakos, E., Atsaves, V., Schlette, E. J., Li, J.-D., Papanastasi, E., Rassidakis, G. Z., & Medeiros, L. J. (2009) · Leukemia · doi:10.1038/leu.2009.180 · Cited by 44
Anticancer effects of the p53 activator nutlin-3 in Ewing’s sarcoma cells
Sonnemann, J., Palani, C. D., Wittig, S., Becker, S., Eichhorn, F., Voigt, A., & Beck, J. F. (2011) · European Journal of Cancer · doi:10.1016/j.ejca.2011.01.015 · Cited by 43
Structurally diverse MDM2–p53 antagonists act as modulators of MDR-1 function in neuroblastoma
Chen, L., Zhao, Y., Halliday, G. C., Berry, P., Rousseau, R. F., Middleton, S. A., NICHOLS, G. L., Bello, F. D., Piergentili, A., Newell, D. R., et al. (2014) · British Journal of Cancer · doi:10.1038/bjc.2014.325 · Cited by 43
p53, SKP2, and DKK3 as MYCN Target Genes and Their Potential Therapeutic Significance
Chen, L., & Tweddle, D. A. (2012) · Frontiers in Oncology · doi:10.3389/fonc.2012.00173 · Cited by 43
Dabiri, Y., el Maaty, M. A. A., Chan, H. Y., Wölker, J., Ott, I., Wölfl, S., & Cheng, X. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00438 · Cited by 44
Tonsing-Carter, E., Bailey, B. J., Saadatzadeh, M. R., Ding, J., Wang, H., Sinn, A. L., Peterman, K. M., Spragins, T. K., Silver, J. M., Sprouse, A. A., et al. (2015) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-15-0237 · Cited by 42
MDM2 mediates p73 ubiquitination: a new molecular mechanism for suppression of p73 function
Wu, H., & Leng, R. P. (2015) · Oncotarget · doi:10.18632/oncotarget.4086 · Cited by 41
Resurrecting a p53 peptide activator - An enabling nanoengineering strategy for peptide therapeutics
He, W., Yan, J., Li, Y., Yan, S., Wang, S., Hou, P., & Lu, W. (2020) · Journal of Controlled Release · doi:10.1016/j.jconrel.2020.06.041 · Cited by 42
Lago, S., Nadai, M., Ruggiero, E., Tassinari, M., Marušič, M., Tosoni, B., Frasson, I., Cernilogar, F. M., Pirota, V., Doria, F., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa1273 · Cited by 41
The Role of MDM2 in Promoting Genome Stability versus Instability
Saadatzadeh, M. R., Elmi, A. N., Pandya, P. H., Bijangi‐Vishehsaraei, K., Ding, J., Stamatkin, C. W., Cohen‐Gadol, A., & Pollok, K. E. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102216 · Cited by 44
Maas, A.-M., Bretz, A. C., Mack, E., & Stiewe, T. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.07.030 · Cited by 43
Gomes, S., Raimundo, L., Soares, J., Loureiro, J. B., Leão, M., Ramos, H., Monteiro, M. N., Lemos, A., Moreira, J., Pinto, M. M. M., et al. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.01.014 · Cited by 39
p73 as a Pharmaceutical Target for Cancer Therapy
Bisso, A., Collavin, L., & Sal, G. D. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211795222667 · Cited by 41
Santag, S., Jäger, W., Karsten, C. B., Kati, S., Pietrek, M., Steinemann, D., Sarek, G., Ojala, P. M., & Schulz, T. F. (2012) · Oncogene · doi:10.1038/onc.2012.385 · Cited by 36
Haaland, I., Opsahl, J. A., Berven, F. S., Reikvam, H., Fredly, H., Haugse, R., Thiede, B., McCormack, E., Laı́n, S., Bruserud, Ø., et al. (2014) · Molecular Cancer · doi:10.1186/1476-4598-13-116 · Cited by 36
JNK–NQO1 axis drives TAp73-mediated tumor suppression upon oxidative and proteasomal stress
Kostecka, A., Sznarkowska, A., Meller, K., Acedo, P., Shi, Y., Sakil, H. A. M., Kawiak, A., Lion, M., Królicka, A., Wilhelm, M., et al. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.408 · Cited by 35
Regulatory feedback loop between TP73 and TRIM32
González-Cano, L., Hillje, A., Fuertes-Álvarez, S., Marqués, M. M., Blanch, A., Ian, R. W., Irwin, M. S., Schwamborn, J. C., & Marín, M. C. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.224 · Cited by 34
The yeast two-hybrid system and its role in drug discovery
Lentze, N., & Auerbach, D. (2008) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.12.4.505 · Cited by 35
Nutlin-3 Affects Expression and Function of Retinoblastoma Protein
Du, W., Wu, J., Walsh, E. M., Zhang, Y., Chen, C. Y., & Xiao, Z.-X. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.046904 · Cited by 33
iASPP Inhibition: Increased Options in Targeting the p53 Family for Cancer Therapy
Bell, H. S., & Ryan, K. M. (2008) · Cancer Research · doi:10.1158/0008-5472.can-08-0182 · Cited by 33
Cyclooxygenase inhibitors differentially modulate p73 isoforms in neuroblastoma
Lau, L. M. S., Wolter, J. K., Lau, J. T. M. L., Cheng, L. S., Smith, K. M., Hansford, L. M., Zhang, L., Baruchel, S., Robinson, F., & Irwin, M. S. (2009) · Oncogene · doi:10.1038/onc.2009.59 · Cited by 33
Jones, R. J., Chen, Q., Voorhees, P. M., Young, K. H., Bruey-Sédano, N., Yang, D., & Orlowski, R. Z. (2008) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-08-0150 · Cited by 31
Carrillo, A. M., Hicks, M., Khabele, D., & Eischen, C. M. (2015) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-15-0089 · Cited by 31
p73: From the p53 shadow to a major pharmacological target in anticancer therapy
Ramos, H., Raimundo, L., & Saraiva, L. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105245 · Cited by 33
Resistance acquisition to MDM2 inhibitors
Cinatl, J., Speidel, D., Hardcastle, I., & Michaelis, M. (2014) · Biochemical Society Transactions · doi:10.1042/bst20140035 · Cited by 30
Novel p53 therapies for head and neck cancer
Castellanos, M. R., & Pan, Q. (2016) · World Journal of Otorhinolaryngology - Head and Neck Surgery · doi:10.1016/j.wjorl.2016.05.005 · Cited by 30
Zanjirband, M., & Rahgozar, S. (2019) · Current Drug Targets · doi:10.2174/1389450120666190402120701 · Cited by 31
Renouf, B., Hollville, É., Pujals, A., Tétaud, C., Garibal, J., & Wiels, J. (2009) · Leukemia · doi:10.1038/leu.2009.92 · Cited by 32
Dey, A., Lane, D. P., & Verma, C. S. (2010) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2010.02.004 · Cited by 27
Carstens, M. R., Fisher, R. C., Acharya, A. P., Butterworth, E. A., Scott, E. W., Huang, E. H., & Keselowsky, B. G. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1505374112 · Cited by 27
Metadata
- Authors
- Lau, L. M. S., Nugent, J. K., Zhao, X., & Irwin, M. S.
- Affiliations
- University of Toronto (CA)
- Corresponding author
- Irwin, M S
- Venue
- Oncogene
- Published
- 2007-08-13
- Volume
- 27
- Issue
- 7
- Pages
- 997-1003
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2029865335
- Cited by
- 182
- References
- 31
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 2 · 2022: 10 · 2021: 7 · 2020: 10 · 2019: 8 · 2018: 5 · 2017: 6 · 2016: 9 · 2015: 11 · 2014: 15 · 2013: 6 · 2012: 18
- FWCI
- 6.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canada Research Chairs
- Terry Fox Foundation
- Hospital for Sick Children
- National Cancer Institute
- 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 › Heat shock proteins research
- Keywords
- Nutlin-3, p73, MDM2, p53-independent apoptosis, Noxa, PUMA, p21, transcriptional activation, p53-null cells, p53 inactivation, cancer therapy
- MeSH terms
- Bone Neoplasms, DNA-Binding Proteins, Humans, Imidazoles, Nuclear Proteins, Piperazines, Protein Binding, Proto-Oncogene Proteins, Osteosarcoma, Transcription, Genetic, Protein Biosynthesis, Immunoblotting, Tumor Suppressor Protein p53, Apoptosis, Proto-Oncogene Proteins c-bcl-2, Tumor Suppressor Proteins, RNA, Small Interfering, HCT116 Cells, Immunoprecipitation, Cyclin-Dependent Kinase Inhibitor p21, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-mdm2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
