Inactivation of the p53 pathway in retinoblastoma
Abstract
Most human tumours have genetic mutations in their Rb and p53 pathways, but retinoblastoma is thought to be an exception. Studies suggest that retinoblastomas, which initiate with mutations in the gene retinoblastoma 1 (RB1), bypass the p53 pathway because they arise from intrinsically death-resistant cells during retinal development. In contrast to this prevailing theory, here we show that the tumour surveillance pathway mediated by Arf, MDM2, MDMX and p53 is activated after loss of RB1 during retinogenesis. RB1-deficient retinoblasts undergo p53-mediated apoptosis and exit the cell cycle. Subsequently, amplification of the MDMX gene and increased expression of MDMX protein are strongly selected for during tumour progression as a mechanism to suppress the p53 response in RB1-deficient retinal cells. Our data provide evidence that the p53 pathway is inactivated in retinoblastoma and that this cancer does not originate from intrinsically death-resistant cells as previously thought. In addition, they support the idea that MDMX is a specific chemotherapeutic target for treating retinoblastoma.
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Elevated MDMX mRNA is detected in 65% of retinoblastomas, and the same percentage of cutaneous melanomas overexpress MDMX protein.
“Elevated levels of levels of MDMX mRNA are detected in 65% of retinoblastomas and the same percentage of cutaneous melanomas overexpress MDMX protein.21,22”
From Mdmx promotes genomic instability independent of p53 and Mdm2 (2015) · cites this paper as [22]
Elevated Mdmx levels are observed in many tumors and during tumorigenesis.
“elevated Mdmx levels are observed in many tumors.3,18–22”
From Mdmx promotes genomic instability independent of p53 and Mdm2 (2015) · cites this paper as [22]
Mutant Mdmx effectively inhibits DNA break repair in human retinal epithelial cells that retain p53 and Arf and frequently overexpress MDMX when transformed, as in retinoblastoma.
“Furthermore, this mutant form of Mdmx effectively inhibited DNA break repair in human retinal epithelial cells, which retain p53 and Arf and frequently overexpress MDMX when transformed, as in retinoblastoma.22”
From Mdmx promotes genomic instability independent of p53 and Mdm2 (2015) · cites this paper as [22]
The MDM4 gene is amplified in 65% of human retinoblastoma.
“Recent data indicate the MDM4 gene is amplified in 65% of human retinoblastoma, a tumor of the eye that often results from inherited mutations in the RB1 gene (MIM#614041) (Laurie, et al., 2006).”
From The Mdm network and its regulation of p53 activities: a rheostat of cancer risk (2014) · cites this paper as Laurie, et al., 2006
About half of lung tumors carry TP53 mutations.
“50% of lung tumors have TP53 mutations”
From The Mdm network and its regulation of p53 activities: a rheostat of cancer risk (2014) · cites this paper as Laurie, et al., 2006
About 65% of retinoblastomas have MDM4 amplification.
“65% of retinoblastomas have MDM4 amplification”
From The Mdm network and its regulation of p53 activities: a rheostat of cancer risk (2014) · cites this paper as Laurie, et al., 2006
Both MDM2 and MDMX can inhibit p53 transactivation by engaging its N-terminal transactivation domain via related hydrophobic pockets.
“Although both MDM2 and MDMX can inhibit p53 transactivation function by engaging its amino-terminal transactivation domain via related N-terminal hydrophobic pockets2,11,12”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [12]
Many tumours exhibit high MDM2 and MDMX protein levels without increased copy number, including melanoma, Ewing's sarcoma, colon carcinoma and retinoblastoma.
“However, many tumours exhibit high MDM2 and MDMX protein levels without increased copy number. These include melanoma10, Ewing's sarcoma22, colon carcinoma9 and retinoblastoma12,23.”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [12]
Retinoblastoma (caused by loss of proteins of the RB tumour suppressor family) is accelerated by MDMX overexpression.
“For example, retinoblastoma (which is caused by the loss of proteins of the RB tumour suppressor family) is accelerated by MDMX overexpression12.”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [12]
Cites
Vogelstein, B., Lane, D., & Levine, A. J. (2000) · Nature · doi:10.1038/35042675 · Cited by 6,607 · see citing works
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 · see citing works
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
Brummelkamp, T. R., Bernards, R., & Agami, R. (2002) · Science · doi:10.1126/science.1068999 · Cited by 4,295 · see citing works
Cancer genes and the pathways they control
Vogelstein, B., & Kinzler, K. W. (2004) · Nature Medicine · doi:10.1038/nm1087 · Cited by 4,245 · see citing works
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 · see citing works
Regulation of p53 stability by Mdm2
Kubbutat, M. H. G., Jones, S. N., & Vousden, K. H. (1997) · Nature · doi:10.1038/387299a0 · Cited by 3,312 · see citing works
Activation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53
Canman, C. E., Lim, D.-S., Cimprich, K. A., Taya, Y., Tamai, K., Sakaguchi, K., Appella, E., Kastan, M. B., & Siliciano, J. D. (1998) · Science · doi:10.1126/science.281.5383.1677 · Cited by 2,042 · see citing works
Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53
Honda, R., Tanaka, H., & Yasuda, H. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01480-4 · Cited by 1,951 · see citing works
Suppression of Human Colorectal Carcinoma Cell Growth by Wild-Type p53
Baker, S. J., Markowitz, S. D., Fearon, E. R., Willson, J. K. V., & Vogelstein, B. (1990) · Science · doi:10.1126/science.2144057 · Cited by 1,742 · see citing works
The RB and p53 pathways in cancer
Sherr, C. J., & McCormick, F. (2002) · Cancer Cell · doi:10.1016/s1535-6108(02)00102-2 · Cited by 1,690 · see citing works
Decision making by p53: life, death and cancer
Oren, M. (2003) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401183 · Cited by 1,063 · see citing works
The MDM2 gene amplification database
Momand, J. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.15.3453 · Cited by 982 · see citing works
Modelling the molecular circuitry of cancer
Hahn, W. C., & Weinberg, R. A. (2002) · Nature reviews. Cancer · doi:10.1038/nrc795 · Cited by 936 · see citing works
Pax6 Is Required for the Multipotent State of Retinal Progenitor Cells
Marquardt, T., Ashery‐Padan, R., Andrejewski, N., Scardigli, R., Guillemot, F., & Gruß, P. (2001) · Cell · doi:10.1016/s0092-8674(01)00295-1 · Cited by 926 · see citing works
Tumor suppression by Ink4a-Arf: progress and puzzles.
Lowe, S. W., & Sherr, C. J. (2003) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(02)00013-8 · Cited by 699 · see citing works
MDMX: a novel p53‐binding protein with some functional properties of MDM2.
Shvarts, A., Steegenga, W. T., Riteco, N., van Laar, T., Dekker, P., Bazuine, M., van Ham, R. C., van der Houven van Oordt, W., Hateboer, G., van der Eb, A. J., et al. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00919.x · Cited by 648 · see citing works
Self-citationSmall molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells
Yang, Y., Ludwig, R. L., Jensen, J. P., Pierre, S. A., Medaglia, M. V., Davydov, I. V., Safiran, Y. J., Oberoi, P., Kenten, J. H., Phillips, A. C., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.029 · Cited by 321 · see citing works
p107 is a suppressor of retinoblastoma development in pRb-deficient micePreprint
Robanus-Maandag, E. C., Dekker, M., van der Valk, M., Carrozza, M. L., Jeanny, J., Dannenberg, J., Berns, A. J. M., & Riele, H. T. (1998) · Genes & Development · doi:10.1101/gad.12.11.1599 · Cited by 319 · see citing works
Danovi, D., Meulmeester, E., Pasini, D., Migliorini, D., Capra, M., Frenk, R., de Graaf, P., Francoz, S., Gasparini, P., Gobbi, A., et al. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.13.5835-5843.2004 · Cited by 310 · see citing works
Self-citationCoordinated regulation of life and death by RB
Chau, B. N., & Wang, J. Y. J. (2003) · Nature Reviews Cancer · doi:10.1038/nrc993 · Cited by 292 · see citing works
Chen, D., Livne-bar, I., Vanderluit, J. L., Slack, R. S., Agochiya, M., & Bremner, R. (2004) · Cancer Cell · doi:10.1016/j.ccr.2004.05.025 · Cited by 281 · 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
The First Knockout Mouse Model of Retinoblastoma
Zhang, J., Schweers, B. A., & Dyer, M. A. (2004) · Cell Cycle · doi:10.4161/cc.3.7.1002 · Cited by 170 · see citing works
Self-citationThe search for the retinoblastoma cell of origin
Dyer, M. A., & Bremmer, R. (2005) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2005.05.013 · Cited by 170 · see citing works
Self-citationThe search for the retinoblastoma cell of origin
Dyer, M. A., & Bremner, R. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1545 · Cited by 170 · see citing works
Self-citationRepression of the Arf tumor suppressor by E2F3 is required for normal cell cycle kineticsPreprint
Aslanian, A., Iaquinta, P. J., Verona, R. I., & Lees, J. A. (2004) · Genes & Development · doi:10.1101/gad.1196704 · Cited by 170 · see citing works
Topotecan Combination Chemotherapy in Two New Rodent Models of Retinoblastoma
Laurie, N. A., Gray, J., Zhang, J., Leggas, M. L., Relling, M. V., Egorin, M. J., Stewart, C. F., & Dyer, M. A. (2005) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-0849 · Cited by 126 · see citing works
Self-citationCompensation by tumor suppressor genes during retinal development in mice and humans
Donovan, S. L., Schweers, B. A., Martins, R. A. P., Johnson, D. A., & Dyer, M. A. (2006) · BMC Biology · doi:10.1186/1741-7007-4-14 · Cited by 104 · see citing works
Self-citationThe 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 · see citing works
ATM&A Key Determinant of Multiple Cellular Responses to Irradiation
Kastan, D.-S. L. M. B. (2001) · Acta Oncologica · doi:10.1080/02841860152619089 · Cited by 70 · see citing works
p53 Regulates Apoptosis in Human Retinoblastoma
Nork, T. M. (1997) · Archives of Ophthalmology · doi:10.1001/archopht.1997.01100150215011 · Cited by 69 · see citing works
Proteomimetic Libraries: Design, Synthesis, and Evaluation of p53−MDM2 Interaction Inhibitors
Lu, F., Chi, S., Kim, D., Han, K., Kuntz, I. D., & Guy, R. K. (2006) · Journal of Combinatorial Chemistry · doi:10.1021/cc050142v · Cited by 68 · see citing works
Loss of heterozygosity on chromosome 17 and mutation of the p53 gene in retinoblastoma
Kato, M. V., Shimizu, T., Ishizaki, K., Kaneko, A., Yandell, D. W., Toguchida, J., & Sasaki, M. S. (1996) · Cancer Letters · doi:10.1016/0304-3835(96)04305-4 · Cited by 60 · see citing works
Use of Preclinical Models to Improve Treatment of Retinoblastoma
Dyer, M. A., Galindo, C. R., & Wilson, M. W. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020332 · Cited by 57 · see citing works
Self-citationMDM2 does not influence p53-mediated sensitivity to DNA-damaging drugs.
McKenzie, P., McPake, C. R., Ashford, A. A., Vanin, E. F., & Harris, L. C. (2002) · PubMed · Cited by 11 · see citing works
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Sorted by citations
MDM2, MDMX and p53 in oncogenesis and cancer therapy
Wade, M., Li, Y.-C., & Wahl, G. M. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3430 · Cited by 1,279 · see citing works
The Cell–Cycle Arrest and Apoptotic Functions of p53 in Tumor Initiation and Progression
Chen, J. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026104 · Cited by 1,222 · see citing works
Awakening guardian angels: drugging the p53 pathway
Brown, C. J., Lain, S., Verma, C. S., Fersht, A. R., & Lane, D. P. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2763 · Cited by 881 · see citing works
Shangary, S., Qin, D., McEachern, D., Liu, M., Miller, R. S., Qiu, S., Nikolovska-Coleska, Z., Ding, K., Wang, G., Chen, J., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708917105 · Cited by 660 · see citing works
Self-citationShangary, S., & Wang, S. (2009) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.48.113006.094723 · Cited by 623 · see citing works
Dimaras, H., Khetan, V., Halliday, W., Orlic, M., Prigoda, N. L., Piovesan, B., Marrano, P., Corson, T. W., Eagle, R. C., Squire, J. A., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn024 · Cited by 351 · see citing works
One hit, two hits, three hits, more? Genomic changes in the development of retinoblastoma
Corson, T. W., & Gallie, B. L. (2007) · Genes, Chromosomes and Cancer · doi:10.1002/gcc.20457 · Cited by 278 · see citing works
MDM2 and MDM4: p53 regulators as targets in anticancer therapy
Toledo, F., & Wahl, G. M. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.03.022 · Cited by 261 · see citing works
Marine, J.-C. W., Dyer, M. A., & Jochemsen, A. G. (2007) · Journal of Cell Science · doi:10.1242/jcs.03362 · Cited by 228 · see citing works
Self-citationIdentification and Characterization of the First Small Molecule Inhibitor of MDMX
Reed, D., Shen, Y., Shelat, A. A., Arnold, L. A., Ferreira, A. M., Zhu, F., Mills, N., Smithson, D. C., Regni, C. A., Bashford, D., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.056747 · Cited by 198 · see citing works
Self-citationDifferentiated Horizontal Interneurons Clonally Expand to Form Metastatic Retinoblastoma in Mice
Ajioka, I., Martins, R. A. P., Bayazitov, I. T., Donovan, S., Johnson, D. A., Frase, S., Cicero, S. A., Boyd, K., Zakharenko, S. S., & Dyer, M. A. (2007) · Cell · doi:10.1016/j.cell.2007.09.036 · Cited by 184 · see citing works
Self-citationHDM2 antagonist Nutlin-3 disrupts p73-HDM2 binding and enhances p73 function
Lau, L. M. S., Nugent, J. K., Zhao, X., & Irwin, M. S. (2008) · Oncogene · doi:10.1038/sj.onc.1210707 · Cited by 182 · see citing works
Phan, J., Li, Z., Kasprzak, A., Li, B., Sebti, S., Guida, W., Schönbrunn, E., & Chen, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.073056 · Cited by 173 · see citing works
Targeting Mdm2 and Mdmx in cancer therapy: better living through medicinal chemistry?
Wade, M., & Wahl, G. M. (2009) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-08-0423 · Cited by 170 · see citing works
Shamma, A., Takegami, Y., Miki, T., Kitajima, S., Noda, M., Obara, T., Okamoto, T., & Takahashi, C. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.03.001 · Cited by 140 · see citing works
Pant, V., Xiong, S., Iwakuma, T., Quintás-Cardama, A., & Lozano, G. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102241108 · Cited by 134 · 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
Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3
LeBron, C., Chen, L., Gilkes, D. M., & Chen, J. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601032 · Cited by 122 · see citing works
Potential for treatment of liposarcomas with the MDM2 antagonist Nutlin-3A
Müller, C. R., Paulsen, E. B., Noordhuis, P., Pedeutour, F., Sæter, G., & Myklebost, O. (2007) · International Journal of Cancer · doi:10.1002/ijc.22643 · Cited by 119 · see citing works
A Small-Molecule Inhibitor of MDMX Activates p53 and Induces Apoptosis
Wang, H., Ma, X., Ren, S., Buolamwini, J. K., & Yan, C. (2011) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-10-0581 · Cited by 117 · see citing works
Ito, M., Barys, L., O'Reilly, T., Young, S., Gorbatcheva, B., Monahan, J., Zumstein-Mecker, S., Choong, P. F., Dickinson, I., Crowe, P., et al. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-2050 · Cited by 115 · see citing works
Shangary, S., Ding, K., Qiu, S., Nikolovska-Coleska, Z., Bauer, J. A., Liu, M., Wang, G., Lu, Y., McEachern, D., Bernard, D., et al. (2008) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-0140 · Cited by 91 · see citing works
Weber, T., Corbett, M. K., Chow, L. M. L., Valentine, M. B., Baker, S. J., & Zuo, J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708061105 · Cited by 89 · 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
Spontaneous Tumorigenesis in Mice Overexpressing the p53-Negative Regulator Mdm4
Xiong, S., Pant, V., Suh, Y.-A., Van Pelt, C. S., Wang, Y., Valentin-Vega, Y. A., Post, S. M., & Lozano, G. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-1457 · Cited by 82 · see citing works
Regulation of MDMX Expression by Mitogenic Signaling
Gilkes, D. M., Pan, Y., Coppola, D., Yeatman, T., Reuther, G. W., & Chen, J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01633-07 · Cited by 82 · see citing works
The Mdm network and its regulation of p53 activities: a rheostat of cancer risk
Eischen, C. M., & Lozano, G. (2014) · Human Mutation · doi:10.1002/humu.22524 · Cited by 79 · see citing works
McEvoy, J., Ulyanov, A., Brennan, R., Wu, G., Pounds, S., Zhang, J., & Dyer, M. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0042739 · Cited by 80 · see citing works
Self-citationWang, Y. V., Leblanc, M., Wade, M., Jochemsen, A. G., & Wahl, G. M. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.05.008 · Cited by 79 · see citing works
Self-citationTranslational approaches targeting the p53 pathway for anti‐cancer therapy
Essmann, F., & Schulze‐Osthoff, K. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01570.x · Cited by 77 · see citing works
Meek, D. W., & Hupp, T. R. (2010) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2009.10.005 · Cited by 76 · see citing works
Loss of <i>Mdm4</i> Results in <i>p53</i> -Dependent Dilated Cardiomyopathy
Xiong, S., Van Pelt, C. S., Elizondo-Fraire, A. C., Fernandez-Garcia, B., & Lozano, G. (2007) · Circulation · doi:10.1161/circulationaha.107.689901 · Cited by 71 · see citing works
Nutlin-3a Is a Potential Therapeutic for Ewing Sarcoma
Pishas, K. I., Al-Ejeh, F., Zinonos, I., Kumar, R., Evdokiou, A., Brown, M. P., Callen, D. F., & Neilsen, P. M. (2011) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-1587 · Cited by 71 · see citing works
Mdmx promotes genomic instability independent of p53 and Mdm2
Carrillo, A. M., Bouska, A., Arrate, M. P., & Eischen, C. M. (2015) · Oncogene · doi:10.1038/onc.2014.27 · Cited by 69 · see citing works
Zhang, F., Tagen, M., Throm, S., Mallari, J., Miller, L., Guy, R. K., Dyer, M. A., Williams, R. T., Roussel, M. F., Nemeth, K., et al. (2011) · Drug Metabolism and Disposition · doi:10.1124/dmd.110.035915 · Cited by 67 · see citing works
Self-citationc-Abl Phosphorylates Hdmx and Regulates Its Interaction with p53
Zuckerman, V., Lenos, K., Popowicz, G. M., Silberman, I., Grossman, T., Marine, J.-C., Holak, T. A., Jochemsen, A. G., & Haupt, Y. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m809211200 · Cited by 68 · see citing works
Self-citationMatijasevic, Z., Steinman, H. A., Hoover, K., & Jones, S. N. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01108-07 · Cited by 58 · see citing works
Vaseva, A. V., Yallowitz, A. R., Marchenko, N. D., Xu, S., & Moll, U. M. (2011) · Cell Death & Disease · doi:10.1038/cddis.2011.39 · Cited by 55 · see citing works
Phillips, A., Teunisse, A., Lam, S., Lodder, K., Darley, M., Emaduddin, M., Wolf, A., Richter, J., de Lange, J., Verlaan-de Vries, M., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.129726 · Cited by 55 · see citing works
Self-citationRole of Mdm4 in drug sensitivity of breast cancer cells
Lam, S., Lodder, K., Teunisse, A. F. A. S., Rabelink, M. J. W. E., Schutte, M., & Jochemsen, A. G. (2010) · Oncogene · doi:10.1038/onc.2009.522 · Cited by 52 · see citing works
Self-citationBH3 activation blocks Hdmx suppression of apoptosis and cooperates with Nutlin to induce cell death
Wade, M., Rodewald, L. W., Espinosa, J. M., & Wahl, G. M. (2008) · Cell Cycle · doi:10.4161/cc.7.13.6072 · Cited by 48 · see citing works
De Clercq, S., Gembarska, A., Denecker, G., Maetens, M., Naessens, M., Haigh, K., Haigh, J. J., & Marine, J.-C. (2010) · Molecular and Cellular Biology · doi:10.1128/mcb.00330-10 · Cited by 35 · see citing works
Self-citationMdmX regulates transformation and chromosomal stability in p53-deficient cells
Matijasevic, Z., Krzywicka-Racka, A., Sluder, G., & Jones, S. N. (2008) · Cell Cycle · doi:10.4161/cc.7.19.6797 · Cited by 34 · see citing works
Cytoplasmic tethering is involved in synergistic inhibition of p53 by Mdmx and Mdm2
Ohtsubo, C., Shiokawa, D., Kodama, M., Gaiddon, C., Nakagama, H., Jochemsen, A. G., Taya, Y., & Okamoto, K. (2009) · Cancer Science · doi:10.1111/j.1349-7006.2009.01180.x · Cited by 32 · see citing works
Abnormal MDMX degradation in tumor cells due to ARF deficiency
Li, X., Gilkes, D., Li, B., Cheng, Q., Pernazza, D., Lawrence, H., Lawrence, N., & Chen, J. (2012) · Oncogene · doi:10.1038/onc.2011.534 · Cited by 32 · see citing works
Valentin-Vega, Y. A., Box, N., Terzian, T., & Lozano, G. (2009) · Differentiation · doi:10.1016/j.diff.2009.03.001 · Cited by 28 · see citing works
Phelps, D., Bondra, K., Seum, S., Chronowski, C., Leasure, J., Kurmasheva, R. T., Middleton, S., Wang, D., Mo, X., & Houghton, P. J. (2015) · Pediatric Blood & Cancer · doi:10.1002/pbc.25465 · Cited by 27 · see citing works
Leventaki, V., Rodic, V., Tripp, S. R., Bayerl, M. G., Perkins, S. L., Barnette, P., Schiffman, J. D., & Miles, R. R. (2012) · British Journal of Haematology · doi:10.1111/j.1365-2141.2012.09243.x · Cited by 26 · see citing works
Lenos, K., de Lange, J., Teunisse, A. F., Lodder, K., Verlaan-de Vries, M., Wiercinska, E., van der Burg, M. J., Szuhai, K., & Jochemsen, A. G. (2011) · Molecular Cancer · doi:10.1186/1476-4598-10-111 · Cited by 16 · see citing works
Self-citation
- Authors
- Laurie, N. A., Donovan, S. L., Shih, C.-S., Zhang, J., Mills, N., Fuller, C., Teunisse, A., Lam, S., Ramos, Y., Mohan, A., Johnson, D., Wilson, M., Rodriguez-Galindo, C., Quarto, M., Francoz, S., Mendrysa, S. M., Kiplin Guy, R., Marine, J.-C., Jochemsen, A. G., & Dyer, M. A.
- Affiliations
- St. Jude Children's Research Hospital (US)
- University of California, San Francisco (US)
- Leiden University Medical Center (NL)
- University of Tennessee Health Science Center (US)
- IFOM (IT)
- Vlaams Instituut voor Biotechnologie (BE)
- Purdue University West Lafayette (US)
- Corresponding author
- Dyer, Michael A.
- ORCID
- Venue
- Nature
- Published
- 2006-11
- Volume
- 444
- Issue
- 7115
- Pages
- 61-66
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2049133549
- Cited by
- 595
- References
- 36
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 17 · 2023: 14 · 2022: 23 · 2021: 19 · 2020: 21 · 2019: 11 · 2018: 16 · 2017: 27 · 2016: 36 · 2015: 34 · 2014: 42 · 2013: 36 · 2012: 49
- FWCI
- 23.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Ophthalmology › Ocular Oncology and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- retinoblastoma, p53 pathway, RB1, MDMX, MDM2, ARF, retinal development, apoptosis, cell cycle exit, tumor surveillance, chemotherapeutic target
- MeSH terms
- Animals, Cell Division, DNA Damage, Gene Amplification, Humans, Imidazoles, Mice, Inbred C57BL, Nuclear Proteins, Piperazines, Proto-Oncogene Proteins, Retina, Retinoblastoma, Tumor Suppressor Protein p53, Retinoblastoma Protein, Cell Death, Rats, Sprague-Dawley, Cell Cycle Proteins, Tumor Suppressor Protein p14ARF, Mice, Rats
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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.
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