The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53
Open accessAbstract
The RING finger proteins HdmX and Hdm2 share significant structural and functional similarity. Hdm2 is a member of the RING finger family of ubiquitin-protein ligases E3 and targets the tumor suppressor protein p53 for degradation. Although HdmX also binds to p53, HdmX does not induce p53 degradation. Moreover, HdmX has been reported to interfere with p53 degradation in overexpression experiments. To obtain insight into the mechanism by which HdmX interferes with p53 degradation, we studied the effect of HdmX on the E3 activity of Hdm2 in vitro. Surprisingly, this revealed that HdmX stimulates Hdm2-mediated ubiquitination of p53 and that HdmX facilitates ubiquitination of Hdm2 and vice versa. In addition, down-regulation of HdmX expression within cells results in the accumulation of both p53 and Hdm2. Because HdmX alone does not have appreciable E3 activity, these data indicate that HdmX acts as a stimulator, rather than as an inhibitor, of the E3 activity of Hdm2 and that, at least under certain conditions, HdmX is actively involved in the degradation of both p53 and Hdm2.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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
“Mdm4 further contributes to Mdm2 stability by disrupting self-ubiquitination of the latter (Stad et al., 2001), while also stimulating Mdm2-mediated polyubiquitination of p53 (Linares et al., 2003).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Linares et al., 2003
In the citing paper
“Despite conservation of the C2H2C4 RING domain, Mdmx shows little intrinsic ubiquitin ligase activity towards p53 [10].”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [10]
In the citing paper
“Together with the observation that the Mdm2–Mdmx hetero-oligomer is a more effective ligase for p53 in vitro than Mdm2 alone [10], this has led to a model in which the Mdm2–Mdmx ligase complex is more efficient in targeting p53 for ubiquitylation and degradation.”
From The p53 orchestra: Mdm2 and Mdmx set the tone (2010) · cites this paper as [10]
In the citing paper
“By contrast, MDMX does not homo-oligomerize and has no intrinsic ubiquitin ligase function, although it can increase or decrease MDM2 ubiquitin ligase activity depending on MDMX abundance16.”
From MDM2, MDMX and p53 in oncogenesis and cancer therapy (2013) · cites this paper as [16]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
Elbashir, S. M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K., & Tuschl, T. (2001) · Nature · doi:10.1038/35078107 · Cited by 9,456
Mdm2 promotes the rapid degradation of p53
Haupt, Y., Maya, R., Kazaz, A., & Oren, M. (1997) · Nature · doi:10.1038/387296a0 · Cited by 4,506
The Ubiquitin-Proteasome Proteolytic Pathway: Destruction for the Sake of Construction
Glickman, M. H., & Ciechanover, A. J. (2002) · Physiological Reviews · doi:10.1152/physrev.00027.2001 · Cited by 4,296
Self-citationRegulation 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
Live or let die: the cell's response to p53
Vousden, K. H., & Lü, X. (2002) · Nature reviews. Cancer · doi:10.1038/nrc864 · Cited by 3,231
Mechanisms Underlying Ubiquitination
Pickart, C. M. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.503 · Cited by 3,184
TAK1 is a ubiquitin-dependent kinase of MKK and IKK
Wang, C., Deng, L., Hong, M., Akkaraju, G. R., Inoue, J.-I., & Chen, Z. J. (2001) · Nature · doi:10.1038/35085597 · Cited by 2,125
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
Recognition of the polyubiquitin proteolytic signal
Thrower, J. S., Hoffman, L. M., Rechsteiner, M., & Pickart, C. M. (2000) · The EMBO Journal · doi:10.1093/emboj/19.1.94 · Cited by 1,769
Themes and variations on ubiquitylation
Weissman, A. M. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056563 · Cited by 1,507
Research works printed but not linked: 2
- Ramos, Y. F., Stad, R., Attema, J., Peltenburg, L. T., van der Eb, A. J. & Jochemsen, A. G. (2001) Cancer Res. 61, 1839–1842.11280734
- Xia, Y., Pao, G., Chen, H. W., Verma, I. M. & Hunter, T. (2002) J. Biol. Chem. 278, 5255–5263.12431996
Cited by
Sorted by citations
RING Domain E3 Ubiquitin Ligases
Deshaies, R. J., & Joazeiro, C. A. P. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.101807.093809 · Cited by 2,679
Malignant astrocytic glioma: genetics, biology, and paths to treatment
Furnari, F. B., Fenton, T., Bachoo, R. M., Mukasa, A., Stommel, J. M., Stegh, A., Hahn, W. C., Ligon, K. L., Louis, D. N., Brennan, C., et al. (2007) · Genes & Development · doi:10.1101/gad.1596707 · Cited by 2,316
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
Kruse, J.-P., & Gu, W. (2009) · Cell · doi:10.1016/j.cell.2009.04.050 · Cited by 1,610
Regulating the p53 pathway: in vitro hypotheses, in vivo veritas
Toledo, F., & Wahl, G. M. (2006) · Nature reviews. Cancer · doi:10.1038/nrc2012 · Cited by 1,286
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
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
Structural insights into the catalysis and regulation of E3 ubiquitin ligases
Buetow, L., & Huang, D. T. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.91 · Cited by 679
A dynamic role of HAUSP in the p53-Mdm2 pathway
Li, M., Brooks, C. L., Kon, N., & Gu, W. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00157-1 · Cited by 679
IAPs, RINGs and ubiquitylation
Vaux, D. L., & Silke, J. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1621 · Cited by 626
Signaling to p53: ribosomal proteins find their way
Zhang, Y., & Lu, H. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.09.024 · Cited by 591
Ubiquitin ligases in oncogenic transformation and cancer therapy
Senft, D., Qi, J., & Ronai, Z. A. (2017) · Nature reviews. Cancer · doi:10.1038/nrc.2017.105 · Cited by 499
The p53 orchestra: Mdm2 and Mdmx set the tone
Wade, M., Wang, Y. V., & Wahl, G. M. (2010) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.01.009 · Cited by 450
Lipkowitz, S., & Weissman, A. M. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3120 · Cited by 422
Adhikary, S., Marinoni, F., Hock, A., Hulleman, E., Popov, N., Beier, R., Bernard, S., Quarto, M., Capra, M. C., Goettig, S., et al. (2005) · Cell · doi:10.1016/j.cell.2005.08.016 · Cited by 403
Self-citationThe 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 408
Keeping p53 in check: essential and synergistic functions of Mdm2 and Mdm4
Marine, J.-C., Francoz, S., Maetens, M., Wahl, G., Toledo, F., & Lozano, G. (2006) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4401912 · Cited by 352
The predator becomes the prey: regulating the ubiquitin system by ubiquitylation and degradation
Weissman, A. M., Shabek, N., & Ciechanover, A. J. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3173 · Cited by 326
Self-citationAkt: A Double-Edged Sword in Cell Proliferation and Genome Stability
Xu, N., Lao, Y., Zhang, Y., & Gillespie, D. A. (2012) · Journal of Oncology · doi:10.1155/2012/951724 · Cited by 307
The multiple levels of regulation by p53 ubiquitination
Lee, J. T., & Gu, W. (2010) · Cell Death & Differentiation · doi:10.1038/cdd.2009.77 · Cited by 289
Linke, K., Mace, P. D., Smith, C. A., Vaux, D. L., Silke, J., & Day, C. L. (2008) · Cell Death & Differentiation · doi:10.1038/sj.cdd.4402309 · Cited by 288
Pathological Unfoldomics of Uncontrolled Chaos: Intrinsically Disordered Proteins and Human Diseases
Uversky, V. N., Davé, V., Iakoucheva, L. M., Malaney, P., Metallo, S. J., Pathak, R. R., & Joerger, A. C. (2014) · Chemical Reviews · doi:10.1021/cr400713r · Cited by 288
The Chaperone-associated Ubiquitin Ligase CHIP Is Able to Target p53 for Proteasomal Degradation
Esser, C., Scheffner, M., & Höhfeld, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501574200 · Cited by 260
Self-citationMdm4 and Mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells in vivo
Francoz, S., Froment, P., Bogaerts, S., De Clercq, S., Maetens, M., Doumont, G., Bellefroid, E., & Marine, J.-C. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508476103 · Cited by 260
Meulmeester, E., Maurice, M. M., Boutell, C., Teunisse, A. F. A. S., Ovaa, H., Abraham, T. E., Dirks, R. W., & Jochemsen, A. G. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.04.024 · Cited by 260
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
Faesen, A. C., Dirac, A. M. G., Shanmugham, A., Ovaa, H., Anastassis Perrakis, A., & Sixma, T. K. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.034 · Cited by 262
Mechanism of p53 stabilization by ATM after DNA damage
Cheng, Q., & Chen, J. (2010) · Cell Cycle · doi:10.4161/cc.9.3.10556 · Cited by 264
MDMX overexpression prevents p53 activation by the MDM2 inhibitor Nutlin
Hu, B., Gilkes, D. M., Farooqi, B., Sebti, S. M., & Chen, J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.c600147200 · Cited by 236
p53 as a target for the treatment of cancer
Duffy, M. J., Synnott, N. C., McGowan, P. M., Crown, J. P., O’Connor, D. P., & Gallagher, W. M. (2014) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2014.10.004 · Cited by 239
Liu, M., Li, C., Pazgier, M., Li, C., Mao, Y., Lv, Y., Gu, B., Wei, G., Yuan, W., Zhan, C., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008930107 · Cited by 236
Marine, J.-C. W., Dyer, M. A., & Jochemsen, A. G. (2007) · Journal of Cell Science · doi:10.1242/jcs.03362 · Cited by 228
Molecular and Genomic Alterations in Glioblastoma Multiforme
Crespo, I., Vital, A. L., Gonzalez-Tablas, M., Patino, M. D. C., Otero, A., Lopes, M. C., de Oliveira, C., Domingues, P., Orfao, A., & Tabernero, M. D. (2015) · The American Journal of Pathology · doi:10.1016/j.ajpath.2015.02.023 · Cited by 225
p53-family proteins and their regulators: hubs and spokes in tumor suppression
Collavin, L., Lunardi, A., & Sal, G. D. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.35 · Cited by 225
Efficient p53 Activation and Apoptosis by Simultaneous Disruption of Binding to MDM2 and MDMX
Hu, B., Gilkes, D. M., & Chen, J. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1140 · Cited by 215
Dayal, S., Sparks, A., Jacob, J., Allende-Vega, N., Lane, D. P., & Saville, M. K. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m805871200 · Cited by 203
Toledo, F., Krummel, K. A., Lee, C. J., Liu, C.-W., Rodewald, L.-W., Tang, M., & Wahl, G. M. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.014 · Cited by 199
The p53 inhibitors MDM2/MDMX complex is required for control of p53 activity in vivo
Huang, L., Yan, Z., Liao, X., Li, Y., Yang, J., Wang, Z.-G., Zuo, Y., Kawai, H., Shadfan, M., Ganapathy, S., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1102309108 · Cited by 193
Mdmx as an essential regulator of p53 activity
Marine, J., & Jochemsen, A. G. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.03.151 · Cited by 189
Protein partners of deubiquitinating enzymes
Ventii, K., & Wilkinson, K. D. (2008) · Biochemical Journal · doi:10.1042/bj20080798 · Cited by 186
Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2
Linares, L. K., Kiernan, R. E., Triboulet, R., Chable-Bessia, C., Latreille, D., Cuvier, O., Lacroix, M., Cam, L. L., Coux, O., & Benkirane, M. (2007) · Nature Cell Biology · doi:10.1038/ncb1545 · Cited by 190
Self-citationRegulation of androgen receptor and histone deacetylase 1 by Mdm2-mediated ubiquitylation
Gaughan, L. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki141 · Cited by 174
The regulation of MDM2 oncogene and its impact on human cancers
Zhao, Y., Yu, H., & Hu, W. (2014) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmt147 · Cited by 181
An essential function of the extreme C-terminus of MDM2 can be provided by MDMX
Uldrijan, S., Pannekoek, W., & Vousden, K. H. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601469 · Cited by 170
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
ATM-Mediated Phosphorylations Inhibit Mdmx/Mdm2 Stabilization by HAUSP in Favor of p53 Activation
Meulmeester, E., Pereg, Y., Shiloh, Y., & Jochemsen, A. G. (2005) · Cell Cycle · doi:10.4161/cc.4.9.1981 · Cited by 173
Limiting the power of p53 through the ubiquitin proteasome pathwayPreprint
Pant, V., & Lozano, G. (2014) · Genes & Development · doi:10.1101/gad.247452.114 · Cited by 170
Saleh, M. N., Patel, M. R., Bauer, T. M., Goel, S., Falchook, G. S., Shapiro, G. I., Chung, K. Y., Infante, J. R., Conry, R. M., Rabinowits, G., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-0715 · Cited by 159
RING Domain–Mediated Interaction Is a Requirement for MDM2's E3 Ligase Activity
Kawai, H., Lopez-Pajares, V., Kim, M. M., Wiederschain, D., & Yuan, Z.-M. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-1313 · Cited by 160
Current strategies to target p53 in cancer
Chen, F., Wang, W., & El‐Deiry, W. S. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.04.031 · Cited by 158
The Rsp5 ubiquitin ligase is coupled to and antagonized by the Ubp2 deubiquitinating enzyme
Kee, Y., Lyon, N., & Huibregtse, J. M. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600710 · Cited by 158
Synergistic roles of Mdm2 and Mdm4 for p53 inhibition in central nervous system development
Xiong, S., Van Pelt, C. S., Elizondo-Fraire, A. C., Liu, G., & Lozano, G. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508500103 · Cited by 155
Systematic Mutational Analysis of Peptide Inhibition of the p53–MDM2/MDMX Interactions
Li, C. V., Pazgier, M., Li, C., Yuan, W., Liu, M., Wei, G., Lu, W., & Lu, W. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.03.005 · Cited by 149
MDMX regulation of p53 response to ribosomal stress
Gilkes, D. M., Chen, L., & Chen, J. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601424 · Cited by 142
Regulation of p53: a collaboration between Mdm2 and MdmX
Pei, D., Zhang, Y., & Zheng, J. (2012) · Oncotarget · doi:10.18632/oncotarget.443 · Cited by 140
Song, M. S., Song, S. J., Kim, S. Y., Oh, H. J., & Lim, D. (2008) · The EMBO Journal · doi:10.1038/emboj.2008.115 · Cited by 137
Glycogen synthase kinase 3-dependent phosphorylation of Mdm2 regulates p53 abundance
Kulikov, R., Boehme, K. A., & Blattner, C. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.16.7170-7180.2005 · 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
Okamoto, K., Kashima, K., Pereg, Y., Ishida, M., Yamazaki, S., Nota, A., Teunisse, A., Migliorini, D., Kitabayashi, I., Marine, J.-C., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.21.9608-9620.2005 · Cited by 129
MDM2 and MDMX: Alone and together in regulation of p53.
Shadfan, M., Lopez-Pajares, V., & Yuan, Z.-M. (2012) · PubMed · Cited by 125
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
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
Quantitative analyses reveal the importance of regulated Hdmx degradation for p53 activation
Wang, Y. V., Wade, M., Wong, E., Li, Y.-C., Rodewald, L. W., & Wahl, G. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701497104 · Cited by 116
MdmX Protein Is Essential for Mdm2 Protein-mediated p53 Polyubiquitination
Wang, X., Wang, J., & Jiang, X. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.213868 · Cited by 121
USP7 Is a Master Regulator of Genome Stability
Valles, G. J., Bezsonova, I., Woodgate, R., & Ashton, N. W. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00717 · Cited by 114
14‐3‐3γ binds to MDMX that is phosphorylated by UV‐activated Chk1, resulting in p53 activation
Jin, Y., Dai, M., Lu, S. Z., Xu, Y., Luo, Z., Zhao, Y., & Lu, H. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601010 · Cited by 116
Mdm2 and MdmX partner to regulate p53
Wang, X., & Jiang, X. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.02.049 · Cited by 117
Novel Dyskerin-Mediated Mechanism of p53 Inactivation through Defective mRNA Translation
Montanaro, L., Calienni, M., Bertoni, S., Rocchi, L., Sansone, P., Storci, G., Santini, D., Ceccarelli, C., Taffurelli, M., Carnicelli, D., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-4024 · Cited by 126
Structure of the Fanconi anaemia monoubiquitin ligase complex
Shakeel, S., Rajendra, E., Alcón, P., O’Reilly, F. J., Chorev, D. S., Maslen, S., Degliesposti, G., Russo, C. J., He, S., Hill, C. H., et al. (2019) · Nature · doi:10.1038/s41586-019-1703-4 · Cited by 107
Identification of ribosomal protein S25 (RPS25)–MDM2–p53 regulatory feedback loop
Zhang, X., Wang, W., Wang, H., Wang, M.-H., Xu, W., & Zhang, R. (2012) · Oncogene · doi:10.1038/onc.2012.289 · Cited by 106
Small-molecule MDM2/X inhibitors and PROTAC degraders for cancer therapy: advances and perspectives
Fang, Y., Liao, G., & Yu, B. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.01.003 · Cited by 106
Targeting prostate cancer based on signal transduction and cell cycle pathways
Lee, J. T., Lehmann, B. D., Terrian, D. M., Chappell, W. H., Stivala, F., Libra, M., Martelli, A. M., Steelman, L. S., & McCubrey, J. A. (2008) · Cell Cycle · doi:10.4161/cc.7.12.6166 · Cited by 104
Lim, S. D., Yim, W. C., Moon, J.-C., Kim, D. S., Lee, B., & Jang, C. S. (2009) · Plant Molecular Biology · doi:10.1007/s11103-009-9576-9 · Cited by 102
Madden, M. M., Muppidi, A., Li, Z., Li, X., Chen, J., & Lin, Q. (2011) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2011.01.004 · Cited by 104
The ubiquitin codes in cellular stress responses
Sheng, X., Xia, Z., Yang, H., & Hu, R. (2023) · Protein & Cell · doi:10.1093/procel/pwad045 · Cited by 117
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
Ribosomal proteins as unrevealed caretakers for cellular stress and genomic instability
Kim, T. H., Leslie, P. L., & Zhang, Y. (2014) · Oncotarget · doi:10.18632/oncotarget.1784 · Cited by 106
Estrada‐Ortiz, N., Neochoritis, C. G., & Dömling, A. S. S. (2015) · ChemMedChem · doi:10.1002/cmdc.201500487 · Cited by 101
Fåhræus, R., & Olivares‐Illana, V. (2013) · Oncogene · doi:10.1038/onc.2013.410 · Cited by 103
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
Phosphatases in the cellular response to DNA damage
Freeman, A. K., & Monteiro, Á. N. A. (2010) · Cell Communication and Signaling · doi:10.1186/1478-811x-8-27 · Cited by 104
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
Mdm2 and Mdm4 Loss Regulates Distinct p53 Activities
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
Stommel, J. M., & Wahl, G. M. (2005) · Cell Cycle · doi:10.4161/cc.4.3.1522 · Cited by 90
Small-molecule inhibitors of MDM2 as new anticancer therapeutics
Dickens, M. P., Fitzgerald, R. P., & Fischer, P. M. (2009) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2009.10.003 · Cited by 90
miR-661 downregulates both Mdm2 and Mdm4 to activate p53
Hoffman, Y., Bublik, D. R., Pilpel, Y., & Oren, M. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.146 · Cited by 88
Glioma oncoprotein Bcl2L12 inhibits the p53 tumor suppressorPreprint
Stegh, A. H., Brennan, C., Mahoney, J. E., Forloney, K. L., Jenq, H. T., Luciano, J. P., Protopopov, A. I., Chin, L., & DePinho, R. A. (2010) · Genes & Development · doi:10.1101/gad.1924710 · Cited by 88
The Fundamental Role of the p53 Pathway in Tumor Metabolism and Its Implication in Tumor Therapy
Shen, L., Sun, X. Y., Fu, Z., Yang, G., Li, J., & Yao, L. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-3040 · Cited by 89
Balance of Yin and Yang: Ubiquitylation-Mediated Regulation of p53 and c-Myc
Dai, M., Jin, Y., Gallegos, J. R., & Lu, H. (2006) · Neoplasia · doi:10.1593/neo.06334 · Cited by 85
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
The role of MDM2 and MDM4 in breast cancer development and prevention
Haupt, S., Vijayakumaran, R., Miranda, P. J., Burgess, A., Lim, E., & Haupt, Y. (2017) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjx007 · Cited by 83
Phosphorylation of MDMX Mediated by Akt Leads to Stabilization and Induces 14-3-3 Binding
Lopez-Pajares, V., Kim, M. M., & Yuan, Z.-M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710030200 · Cited by 79
Nie, J., Xie, P., Liu, L., Xing, G., Chang, Z., Yin, Y., Tian, C., He, F., & Zhang, L. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.126920 · Cited by 79
Translational 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
Mdmx enhances p53 ubiquitination by altering the substrate preference of the Mdm2 ubiquitin ligase
Okamoto, K., Taya, Y., & Nakagama, H. (2009) · FEBS Letters · doi:10.1016/j.febslet.2009.07.021 · Cited by 76
Iron-Dependent Regulation of MDM2 Influences p53 Activity and Hepatic Carcinogenesis
Dongiovanni, P., Fracanzani, A. L., Cairo, G., Megazzini, C., Gatti, S., Rametta, R., Fargion, S. R., & Valenti, L. V. C. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2010.090249 · Cited by 72
Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity
Nomura, K., Klejnot, M., Kowalczyk, D., Hock, A. K., Sibbet, G. J., Vousden, K. H., & Huang, D. T. C. (2017) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3414 · Cited by 72
FL118 Induces p53-Dependent Senescence in Colorectal Cancer Cells by Promoting Degradation of MdmX
Ling, X., Xu, C., Fan, C., Zhong, K. L., Li, F., & Wang, X. (2014) · Cancer Research · doi:10.1158/0008-5472.can-14-0683 · Cited by 70
Singh, R. K., Iyappan, S., & Scheffner, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610879200 · Cited by 69
Self-citationDysregulation of ubiquitin ligases in cancer
Qi, J., & Ronai, Z. A. (2015) · Drug Resistance Updates · doi:10.1016/j.drup.2015.09.001 · Cited by 69
Metadata
- Authors
- Linares, L. K., Hengstermann, A., Ciechanover, A., Müller, S., & Scheffner, M.
- Affiliations
- Center for Biochemistry, Medical Faculty, and Center for Molecular Medicine, University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Cologne, Germany; and Department of Biochemistry and The Rappaport Family Institute for Research in the Medical Sciences, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel
- Technion – Israel Institute of Technology (IL)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2003-09-24
- Volume
- 100
- Issue
- 21
- Pages
- 12009-12014
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC218704
- OpenAlex
- W2046135777
- Cited by
- 361
- References
- 38
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 5 · 2023: 11 · 2022: 15 · 2021: 17 · 2020: 17 · 2019: 14 · 2018: 10 · 2017: 16 · 2016: 16 · 2015: 12 · 2014: 30 · 2013: 19 · 2012: 30
- FWCI
- 4.81
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- KOPS (University of Konstanz) (submittedVersion)
- Funders
- German-Israeli Foundation for Scientific Research and Development
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Keywords
- HDMX, MDM2, p53 degradation, ubiquitination, E3 ubiquitin ligase, RING finger protein, protein degradation, tumor suppressor, protein-protein interaction, p53 accumulation
- MeSH terms
- Amino Acid Sequence, Base Sequence, Cell Line, Humans, Molecular Sequence Data, Nuclear Proteins, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Transfection, Tumor Suppressor Protein p53, Ubiquitin, RNA, Small Interfering, Ubiquitin-Protein Ligases, Proto-Oncogene Proteins c-mdm2, In Vitro Techniques
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
