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MdmX Protects p53 from Mdm2-Mediated Degradation
Open accessAbstract
The p53 tumor suppressor protein is stabilized in response to cellular stress, resulting in activation of genes responsible for either cell cycle arrest or apoptosis. The cellular pathway for releasing normal cells from p53-dependent cell cycle arrest involves the Mdm2 protein. Recently, a p53-binding protein with homology to Mdm2 was identified and called MdmX. Like Mdm2, MdmX is able to bind p53 and inhibit p53 transactivation; however, the ability of MdmX to degrade p53 has yet to be examined. We report here that MdmX is capable of associating with p53 yet is unable to facilitate nuclear export or induce p53 degradation. In addition, expression of MdmX can reverse Mdm2-targeted degradation of p53 while maintaining suppression of p53 transactivation. Using a series of MdmX deletions, we have determined that there are two distinct domains of the MdmX protein that can stabilize p53 in the presence of Mdm2. One domain requires MdmX interaction with p53 and results in the retention of both proteins within the nucleus and repression of p53 transactivation. The second domain involves the MdmX ring finger and results in stabilization of p53 and an increase in p53 transactivation. The potential basis for stabilization and increased p53 transactivation by the MdmX ring finger domain is discussed. Based on these observations, we propose that the MdmX protein may function to maintain a nuclear pool of p53 protein in undamaged cells.
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“However, Mdmx does not target p53 for degradation but even prevents Mdm2-mediated degradation of p53 and also stabilizes Mdm2 (Sharp et al., 1999;Jackson and Berberich, 2000;Stad et al., 2000).”
From Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms (2001) · cites this paper as Jackson and Berberich, 2000
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“Since Mdmx is unable to shuttle from the nucleus to the cytoplasm (Jackson and Berberich, 2000)”
From Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms (2001) · cites this paper as Jackson and Berberich, 2000
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p53 ubiquitination by Mdm2: A never ending tail?
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Levav-Cohen, Y., Goldberg, Z., Zuckerman, V., Grossman, T., Haupt, S., & Haupt, Y. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.03.152 · Cited by 57
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Assay for Ubiquitin Ligase Activity: High-Throughput Screen for Inhibitors of HDM2
Davydov, I. V., Woods, D. B., Safiran, Y. J., Oberoi, P., Fearnhead, H. O., Fang, S., Jensen, J. P., Weissman, A. M., Kenten, J. H., & Vousden, K. H. (2004) · SLAS DISCOVERY · doi:10.1177/1087057104267956 · Cited by 55
Sarkari, F., La Delfa, A., Arrowsmith, C. H., Frappier, L., Sheng, Y., & Saridakis, V. (2010) · Journal of Molecular Biology · doi:10.1016/j.jmb.2010.08.017 · Cited by 54
Stability of nucleolar versus non-nucleolar forms of human p14ARF
RODWAY, H. A., Llanos, S., Rowe, J., & Peters, G. G. (2004) · Oncogene · doi:10.1038/sj.onc.1207854 · Cited by 53
“As a control, we used a mutant form of MDMX (MDMXR-) that lacks the C-terminal ring finger and is therefore unable to associate with MDM2 (Jackson and Berberich, 2000; Migliorini et al., 2002).”
MethodRescue of Mdm4-deficient mice by Mdm2 reveals functional overlap of Mdm2 and Mdm4 in development
Steinman, H. A., Hoover, K. L., Keeler, M. L., Sands, A., & Jones, S. N. (2005) · Oncogene · doi:10.1038/sj.onc.1208930 · 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
Rallapalli, R., Strachan, G. D., Tuan, R. S., & Hall, D. J. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10535 · Cited by 45
Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice
Qu, J., Yang, S., Zhu, Y., Guo, T., Thannickal, V. J., & Zhou, Y. (2021) · The Journal of Experimental Medicine · doi:10.1084/jem.20202033 · Cited by 45
DisruptingTP53 in mouse models of human cancers
Parant, J. M., & Lozano, G. (2003) · Human Mutation · doi:10.1002/humu.10186 · Cited by 47
Structural and Functional Comparison of the RING Domains of Two p53 E3 Ligases, Mdm2 and Pirh2
Shloush, J., Vlassov, J. E., Engson, I., Duan, S., Saridakis, V., Dhe-paganon, S., Raught, B., Sheng, Y., & Arrowsmith, C. H. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.157669 · Cited by 42
Cooperative Roles of c-Abl and Cdk5 in Regulation of p53 in Response to Oxidative Stress
Lee, J., Jeong, M.-W., Kim, W., Choi, Y. H., & Kim, K. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m706201200 · Cited by 43
MDMX Recruits UbcH5c to Facilitate MDM2 E3 Ligase Activity and Subsequent p53 Degradation In Vivo
Yang, J., Jin, A., Han, J., Chen, X., Zheng, J., & Zhang, Y. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-0790 · Cited by 39
“Other studies have shown that overexpression of MDMX can stabilize p53 and reverse MDM2-mediated p53 degradation (9), and thatMDMX increases MDM2 levels by reducingMDM2 E3 ligase activity toward itself (10).”
MdmX inhibits Smad transactivation
Kadakia, M., Brown, T. L., McGorry, M. M., & Berberich, S. J. (2002) · Oncogene · doi:10.1038/sj.onc.1205993 · Cited by 39
“Expression plasmids encoding mdm2, mdmX and various mdmX deletions were constructed as previously described (Jackson and Berberich, 2000). mdmx CtCC represents a deletion mutant lacking the first 364 amino acid residues cloned into pFLAG-CMV2.”
BackgroundMethodResultInfluentialSelf-citationOtub1 stabilizes MDMX and promotes its proapoptotic function at the mitochondria
Chen, Y., Wang, Y.-G., Li, Y., Sun, X., & Dai, M. (2016) · Oncotarget · doi:10.18632/oncotarget.14278 · Cited by 38
“Unlike MDM2, MDMX does not possess ubiquitin E3 activity towards p53 [24, 25].”
BackgroundMDM4 (MDMX) Overexpression Enhances Stabilization of Stress-induced p53 and Promotes Apoptosis
Mancini, F., Gentiletti, F., D'Angelo, M., Giglio, S., Nanni, S., D’Angelo, C., Farsetti, A., Citro, G., Sacchi, A., Pontecorvi, A., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311793200 · Cited by 38
Boutell, C., & Everett, R. D. (2004) · Journal of Virology · doi:10.1128/jvi.78.15.8068-8077.2004 · Cited by 42
“Stabilization of p53 can occur through several mechanisms, including phosphorylation of p53 at Nterminal serine (Ser) and threonine (Thr) residues (6, 41, 68, 69); acetylation of C-terminal lysine residues (38, 47); phosphorylation (15, 35, 42, 53) and sequestration of Mdm2 (40, 49, 61, 73, 83); and competitive bindin…”
BackgroundMDM2 and MDMX in Cancer and Development
Marine, J. (2011) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-380916-2.00003-6 · Cited by 39
Harmonic Oscillations in Homeostatic Controllers: Dynamics of the p53 Regulatory System
Jolma, I. W., Ni, X. Y., Rensing, L., & Ruoff, P. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2009.11.013 · Cited by 35
“In addition, MdmX has been shown to bind to both Mdm2 and p53, which stabilizes each of these species (58).”
BackgroundMDMX stability is regulated by p53-induced caspase cleavage in NIH3T3 mouse fibroblasts
Gentiletti, F., Mancini, F., D'Angelo, M., Sacchi, A., Pontecorvi, A., Jochemsen, A. G., & Moretti, F. (2002) · Oncogene · doi:10.1038/sj.onc.1205137 · Cited by 36
“In analogy, MDMX has been shown able to bind p53 and, when overexpressed, also to inhibit its transactivating function (Shvarts et al., 1996; Rallapalli et al., 1999; Bottger et al., 1999; Jackson and Berberich, 2000).”
BackgroundResultInfluentialCarr, M. I., Roderick, J. E., Gannon, H., Kelliher, M. A., & Jones, S. N. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.08.014 · Cited by 34
Adenoviral E1A Targets Mdm4 to Stabilize Tumor Suppressor p53
Li, Z., Day, C., Yang, J.-Y., Tsai, W.-B., Lozano, G., Shih, H.-M., & Hung, M. (2004) · Cancer Research · doi:10.1158/0008-5472.can-04-2419 · Cited by 33
“Because Mdm4 can interact with Mdm2 and p53 (11, 26), we examined whether Mdm4 binding activity of E1A could disrupt the interaction between Mdm4 and Mdm2 by cotransfection and immunoprecipitation (Fig.”
BackgroundInhibitors of MDM2 and MDMX: A Structural Perspective
Riedinger, C., & McDonnell, J. M. (2009) · Future Medicinal Chemistry · doi:10.4155/fmc.09.75 · Cited by 32
Boultwood, J., Pellagatti, A., & Wainscoat, J. S. (2011) · Advances in Biological Regulation · doi:10.1016/j.advenzreg.2011.09.008 · Cited by 32
Substrate Phosphorylation and Feedback Regulation in JFK-promoted p53 Destabilization
Sun, L., Shi, L., Wang, F., Huangyang, P., Si, W., Yang, J., Yao, Z., & Shang, Y. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.195115 · Cited by 32
Kulkarni, D. A., Vázquez, A., Haffty, B. G., Bandera, E. V., Hu, W., Sun, Y., Toppmeyer, D., Levine, A. J., & Hirshfield, K. M. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp224 · Cited by 33
“While it has been reported that overexpression of MDM4 inhibits MDM2-mediated p53 degradation thus stabilizing p53, [8-11], there is also evidence that MDM4 stimulates MDM2-mediated p53 ubiquitination, MDM2 autoubiquitination [12], and contributes to MDM2 E3 ubiquitin ligase activity [13,14].”
Backgroundc-Abl Phosphorylation of Mdm2 Facilitates Mdm2-Mdmx Complex Formation
Waning, D. L., Lehman, J. A., Batuello, C. N., & Mayo, L. D. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.183012 · Cited by 30
Kojima, T., Ikawa, Y., & Katoh, I. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.4486 · Cited by 29
Yoon, K., Zhu, S., Ewing, S. J., & Smart, R. C. (2006) · Oncogene · doi:10.1038/sj.onc.1209797 · Cited by 28
“MdmX can form dimers with Mdm2 and stabilize p53 (Jackson and Berberich, 2000).”
BackgroundFunctional analysis of p53 tumor suppressor in yeast
Šmardová, J., Šmarda, J., & Koptíková, J. (2005) · Differentiation · doi:10.1111/j.1432-0436.2005.00028.x · Cited by 29
Valentin-Vega, Y. A., Box, N., Terzian, T., & Lozano, G. (2009) · Differentiation · doi:10.1016/j.diff.2009.03.001 · Cited by 28
“An important observation from our study is that loss of Mdm4 in the intestinal epithelium leads to increased p53 levels in the proliferative compartment exclusively, yet Mdm4 is not an E3 ubiquitin ligase (Jackson & Berberich 2000, Sharp et al 1999).”
BackgroundChen, J., Zhang, D., Zhang, Y., & Li, G. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms13022176 · Cited by 27
“Previous insights into the inhibition of the p53-MDM2/MDMX interaction also reveal that the most of the peptide and non-peptide inhibitors, such as Nutlins and MI-219, provide strong anti-tumor potential of MDM2 inhibitors, but they do not efficiently inhibit the interaction of MDMX with p53 [6,14–24].”
Jung, J. H., Lee, H., Zeng, S. X., & Lu, H. (2020) · Cells · doi:10.3390/cells9092107 · Cited by 27
“Intriguingly, MDMX itself is a substrate of the MDM2 E3 ligase, thus acting as a competitive substrate for polyubiquitination against p53 [47,50,51].”
BackgroundUsing Mouse Models to Explore MDM-p53 Signaling in Development, Cell Growth, and Tumorigenesis
Gannon, H., & Jones, S. N. (2012) · Genes & Cancer · doi:10.1177/1947601912455324 · Cited by 25
“However, in vitro studies have determined that MDMX does not mediate p53 protein degradation, suggesting that MDMX inhibits p53 activity solely through steric inhibition of p53 transcriptional activity.(47,48) Several groups have generated MdmX-null alleles in mice.”
BackgroundRequirement for HDM2 Activity in the Rapid Degradation of p53 in Neuroblastoma
Isaacs, J. S., Saito, S., & Neckers, L. Μ. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100638200 · Cited by 25
Markey, M. P. (2010) · Frontiers in bioscience · doi:10.2741/3780 · Cited by 26
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“can heterodimerize with Hdm2 [8, 9], HdmX lacks the ability to ubiquitinate p53 in vivo [10, 11] and thus can only antagonize p53 transactivation [12].”
Self-citationThe roles of mouse double minute 2 (MDM2) oncoprotein in ocular diseases: A review
Jiang, H., Luo, J., & Lei, H. (2022) · Experimental Eye Research · doi:10.1016/j.exer.2021.108910 · Cited by 23
Mdm2 inhibition of p53 induces E2F1 transactivation via p21
Wunderlich, M., & Berberich, S. J. (2002) · Oncogene · doi:10.1038/sj.onc.1205541 · Cited by 23
“1-lacz (Jackson and Berberich, 1999, 2000; Jackson et al., 2001). pGL3LUC (Promega), pR-Luc (Promega) and pEGFPN1 (Clontech) were purchased from the indicated vendors. pRcHA-E2F1 and pcDNA3.”
MethodSelf-citationTumor suppressor p53 and estrogen receptors in nuclear–mitochondrial communication
Wickramasekera, N. T., & Das, G. M. (2013) · Mitochondrion · doi:10.1016/j.mito.2013.10.002 · Cited by 24
“This suggests that MdmX is in fact playing a protective role towards p53 from Mdm2-mediated suppression (Jackson and Berberich, 2000).”
BackgroundMDM4 enhances p53 stability by promoting an active conformation of the protein upon DNA damage
Conza, G. D., Mancini, F., Buttarelli, M., Pontecorvi, A., Trimarchi, F., & Moretti, F. (2012) · Cell Cycle · doi:10.4161/cc.11.4.19208 · Cited by 21
The Potential of Targeting P53 and HSP90 Overcoming Acquired MAPKi-Resistant Melanoma
Hsieh, C., & Shen, C. (2019) · Current Treatment Options in Oncology · doi:10.1007/s11864-019-0622-9 · Cited by 20
Mouse modelling of the MDM2/MDMX−p53 signalling axis
Tackmann, N. R., & Zhang, Y. (2017) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjx006 · Cited by 21
“, 1996), but unlike MDM2, MDMX does not harbour E3 ubiquitin ligase activity (Jackson and Berberich, 2000).”
BackgroundInfluentialOncoprotein stabilization in brain tumors
Hede, S.-M., Savov, V., Weishaupt, H., Sangfelt, O., & Swartling, F. J. (2013) · Oncogene · doi:10.1038/onc.2013.445 · Cited by 20
Touqan, N., Diggle, C. P., Verghese, E. T., Perry, S., Horgan, K. J., Merchant, W., Anwar, R., Markham, A. F., Carr, I., & Achuthan, R. (2013) · BMC Clinical Pathology · doi:10.1186/1472-6890-13-32 · Cited by 18
“This pattern may be explained by MDMX possibly “competing” with MDM2 in binding to P53, resulting in reduced P53 degradation by MDM2 and therefore higher cellular expression levels, in line with MDMX acting, here, as a P53 stabiliser [16,37].”
BackgroundExpanding the horizon of chemotherapeutic targets: From MDM2 to MDMX (MDM4)
Macchiarulo, A., Giacchè, N., Carotti, A., Moretti, F., & Pellicciari, R. (2011) · MedChemComm · doi:10.1039/c0md00238k · Cited by 16
Predicted Functions of MdmX in Fine-Tuning the Response of p53 to DNA Damage
Kim, S., Aladjem, M. I., McFadden, G. B., & Kohn, K. W. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000665 · Cited by 16
“It was previously speculated that p53:MdmX heterodimer may serve as a reservoir to maintain a pool of p53 [44].”
Balmer, M. T., Katz, R. D., Liao, S., Goodwine, J. S., & Gal, S. (2014) · Cancer Biology & Therapy · doi:10.4161/cbt.29112 · Cited by 16
“Interestingly, MdmX is also ubiquitinated by Mdm2(30) and has been proposed to inhibit Mdm2-mediated p53 degradation by competing with p53 for Mdm2 binding.(48,49) Consistent with that, we found that the level of MdmX goes down after drug treatment and this drop is Figure 7.”
BackgroundA Transcriptionally Inactive E2F-1 Targets the MDM Family of Proteins for Proteolytic Degradation
Strachan, G. D., Rallapalli, R., Pucci, B., Lafond, T. P., & Hall, D. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103765200 · Cited by 16
p53 Pathway Alterations in Brain Tumors
Yin, S., & Meir, E. G. V. (2009) · Humana Press eBooks · doi:10.1007/978-1-60327-553-8_14 · Cited by 15
Matijašević, Z., Krzywicka-Racka, A., Sluder, G., Gallant, J., & Jones, S. N. (2016) · Oncogenesis · doi:10.1038/oncsis.2016.62 · Cited by 14
Mdm2 and MdmX Involvement in Human Cancer
Berberich, S. J. (2014) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-94-017-9211-0_15 · Cited by 12
“While MdmX alone does not impact p53 stability [92] it is able to bind to p53 with affinities comparable to Mdm2 [11] and thus inhibit p53 transactivation [42].”
BackgroundSelf-citationRole of the N-terminal lid in regulating the interaction of phosphorylated MDMX with p53
Chan, J. V., Koh, D. X. P., Liu, Y., Joseph, T. L., Lane, D. P., Verma, C. S., & Tan, Y. S. (2017) · Oncotarget · doi:10.18632/oncotarget.22829 · Cited by 12
“However, unlike MDM2, MDMX is unable to target p53 for proteolysis or induce its nuclear export [8].”
Molecular Targeting of the Most Functionally Complex Gene in Precision Oncology: p53
Brown, D. W., Beatty, P. H., & Lewis, J. D. (2022) · Cancers · doi:10.3390/cancers14215176 · Cited by 13
“A structurally homologous protein, MDMX/MDM4, has a similar role to MDM2 in negatively regulating p53 activity, except MDMX is not an E3-ubiquitin ligase and instead inhibits p53 transcriptional activity by physical association [40,41].”
BackgroundCircumvention and reactivation of the p53 oncogene checkpoint in mouse colon tumors
Aizu, W., Belinsky, G. S., Flynn, C. M., Noonan, E. J., Boes, C. C., Godman, C. A., Doshi, B. M., Nambiar, P. R., Rosenberg, D. W., & Giardina, C. A. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.07.009 · Cited by 13
p53 Selectively Regulates Developmental Apoptosis of Rod Photoreceptors
Vuong, L., Brobst, D. E., Ivanovic, I., Sherry, D. M., & Al‐Ubaidi, M. R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067381 · Cited by 11
p53 – ein natürlicher Krebskiller: Einsichten in die Struktur und Therapiekonzepte
Römer, L., Klein, C., Dehner, A., Kessler, H., & Büchner, J. (2006) · Angewandte Chemie · doi:10.1002/ange.200600611 · Cited by 12
Gα12/13 Basally Regulates p53 through Mdm4 Expression
Kim, M.-S., Lee, S. M., Kim, W., Ki, S. H., Moon, A., Lee, C. H., & Kim, S. G. (2007) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-06-0395 · Cited by 10
“Regulation of Mdm4 by Ga12/13 Mdm4 is a p53-binding protein that antagonizes the activity of mdm2, stabilizing p53 (34, 35).”
BackgroundMiyagi, Y. (2011) · Oncology Reports · doi:10.3892/or.2011.1270 · Cited by 10
“However, the function of MDM4 is still controversial, because it has been reported that MDM4 binds directly to p53 and inhibits its transcriptional activity (12), and also that overexpression of MDM4 interferes with the ubiquitin ligase activity of MDM2 (13,14).”
Hainaut, P. L., Wiman, K. G., & Olivier, M. (2012) · Springer eBooks · doi:10.1007/978-1-4614-3676-8 · Cited by 10
Mdm2 and mdmX prevent ASPP1 and ASPP2 from stimulating p53 without targeting p53 for degradation
Bergamaschi, D., Samuels, Y., Zhong, S., & Lü, X. (2005) · Oncogene · doi:10.1038/sj.onc.1208535 · Cited by 10
“In agreement with this, the coexpression of mdmx, a family member of mdm2, which can bind p53 without targeting it for degradation (Jackson and Berberich, 2000; Stad et al., 2001), inhibited the apoptotic function of p53.”
BackgroundInactivation of the MDM2 RING domain enhances p53 transcriptional activity in mice
Tian, H., Tackmann, N. R., Jin, A., Zheng, J., & Zhang, Y. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.ra117.000122 · Cited by 9
“Since the MDM2 mutation disrupts MDM2-MDMX interaction and MDMX has been shown to be important for MDM2-mediated p53 regulation (24-26), we”
Backgroundp53 Regulation Goes Live--Mdm2 and MdmX Co-Star: Lessons Learned from Mouse Modeling
Tollini, L. A., & Zhang, Y. (2012) · Genes & Cancer · doi:10.1177/1947601912454732 · Cited by 9
The RING Finger Domain of MDM2 Is Essential for MDM2-mediated TGF-β Resistance
Kannemeier, C., Liao, R., & Sun, P. (2007) · Molecular Biology of the Cell · doi:10.1091/mbc.e06-09-0844 · Cited by 8
“It has been reported that in both murine and human cells, MDMX stabilizes p53 protein, possibly by competing with MDM2 for p53 binding and inhibiting the degradation of p53 by MDM2 (Jackson and Berberich, 2000; Stad et al., 2000; Gu et al., 2002).”
BackgroundGatekeepers of the Guardian: p53 Regulation by Post-Translational Modification, MDM2 and MDMX
Wahl, G. M., Stommel, J. M., Krummel, K. A., & Wade, M. R. (2005) · Springer eBooks · doi:10.1007/978-1-4020-2922-6_4 · Cited by 9
“Several studies employing transfection and overexpression indicated that MDMX can inhibit p53 degradation (Jackson and Berberich, 2000; Sharp et al., 1999; Stad et al., 2001).”
BackgroundSanford, J. D., Yang, J., Han, J., Tollini, L. A., Jin, A., & Zhang, Y. (2021) · BMC Molecular and Cell Biology · doi:10.1186/s12860-021-00385-3 · Cited by 7
“It has also been suggested that MDMX can increase p53 stability by inhibiting MDM2 following DNA damage and nuclear translocation [9, 29].”
BackgroundInfluentialSHORT REPORT Potential for treatment of liposarcomas with the MDM2 antagonist Nutlin-3A
Paulsen, E. B., Noordhuis, P., Pédeutour, F., Sæter, G., & Myklebost, O. (2007) · Cited by 5
MDM2: RING Finger Protein and Regulator of p53
Wu, L., & Maki, C. G. (2005) · Springer eBooks · doi:10.1007/0-387-27421-9_34 · Cited by 4
Longerich, T. (2014) · Der Pathologe · doi:10.1007/s00292-014-2007-y · Cited by 2
Cooperation between MDM2 and MDMX in the Regulation of p53
Blaydes, J. P. (2010) · Molecular biology intelligence unit · doi:10.1007/978-1-4419-8231-5_6 · Cited by 2
Mutant p53-Driven Tumorigenesis
Terzian, T., & Lozano, G. (2012) · Springer eBooks · doi:10.1007/978-1-4614-3676-8_5 · Cited by 2
Klotzbücher, A., & Kubbutat, M. H. G. (2002) · Cancer drug discovery and develogment/Cancer drug discovery and development · doi:10.1007/978-1-59259-153-4_10 · Cited by 1
Novel approaches to the treatment of high-grade sarcoma
Müller, C. R. (2011) · NORA - Norwegian Open Research Archives · Cited by 1
Tumor suppressor p53 and transcriptional changes in cellular stress responses to UV radiation
Latonen, L. (2003) · Työväentutkimus Vuosikirja
Small Molecules as Research Tools for Studying the Biology of the Tumour Suppressor p53
Spinnler, C. (2011) · Figshare
Regulation of the p53 Tumor‐Suppressor Protein by Ubiquitin and Ubiquitin‐Like Molecules
Xirodimas, D. P. (2007) · Wiley eBooks · doi:10.1002/9783527619320.ch2c
Multiple modes of Mdmx regulation affect p53 activation
Gilkes, D. M. (2008) · Digital Commons - University of South Florida (University of South Florida)
Touqan, N. (2014) · UPT. Syiah Kuala University Library (Syiah Kuala University)
Adenovirus and its interaction with host cell proteins
Carr, S. (2007) · St Andrews Research Repository (St Andrews Research Repository)
Modulation of p53 activities by the prolyl-isomerase PIN1 and the bromodomain protein BRD7
Tocco, F. (2008) · OpenstarTs (Univeristy of Trieste https://www.units.it/)
Post-translational Modifications of the p53 Transcription Factor
Brooks, C. L., & Gu, W. J. (2007) · Springer eBooks · doi:10.1007/978-0-387-40049-5_15
Modification of MDMX by Ubiquitination and Sumoylation
Pan, Y. (2005) · Digital Commons - University of South Florida (University of South Florida)
p53 and DNA damage checkpoint responses in the human prostate
af Hällström, T. (2007)
Hosako, H. (2009) · OakTrust (Texas A&M University Libraries)
Characterization of the Ubiquitin/Nedd8 E3 ligase activity of the Mdm2/MdmX complex
Singh, R. K. (2007) · Kölner Universitäts PublikationsServer (Universität zu Köln)
Cellular Changes and Effects of Cytokines in the Transformation of Human Mammary Epithelial Cells
Kan, C. E. (2009) · OhioLink ETD Center (Ohio Library and Information Network)
p53 Tumor Suppressor Opens Gateways for Cancer Therapy
Dai, M., Gallegos, J. R., & Lu, H. (2008) · CRC Press eBooks · doi:10.1201/9780849387999.ch48
Husaini, R. (2014) · Bradford Scholars (University of Bradford)
Passenger or Driver: Can Gene Expression Profiling Tell Us Anything about LINE-1 in Cancer?
Ohms, S., Dahlstrom, J. E., & Rangasamy, D. (2018) · InTech eBooks · doi:10.5772/intechopen.73266 · Cited by 1
“MDM4 binds p53 although it has no intrinsic ubiquitin ligase activity [195].”
BackgroundIn Vivo Discoveries in MDM2-Mediated p53 Regulation
Tackmann, N. R. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/z7ta-7m83
Friedberg, E. C., Walker, G. C., Siede, W., Wood, R. D., Schultz, R. A., & Ellenberger, T. E. (2014) · ASM Press eBooks · doi:10.1128/9781555816704.ch21
Metadata
- Authors
- Jackson, M. W., & Berberich, S. J.
- Affiliations
- Wright State University (US)
- ORCID
- Jackson, Mark W.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-02-01
- Volume
- 20
- Issue
- 3
- Pages
- 1001-1007
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC85217
- OpenAlex
- W2125124408
- Cited by
- 211
- References
- 35
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 4 · 2014: 11 · 2013: 5 · 2012: 14
- FWCI
- 7.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (CA-64430, R01CA064430, R29CA064430)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Keywords
- MDMX, p53, MDM2, p53 degradation, p53 stabilization, p53 transactivation, RING domain, nuclear retention, tumor suppressor proteins, cell cycle arrest, apoptosis
- MeSH terms
- Amino Acid Sequence, Animals, Carcinoma, Non-Small-Cell Lung, Cell Line, Cell Nucleus, HeLa Cells, Humans, Lung Neoplasms, Molecular Sequence Data, Nuclear Proteins, Proto-Oncogene Proteins, Recombinant Proteins, Transfection, Tumor Cells, Cultured, Transcriptional Activation, Genes, p53, Tumor Suppressor Protein p53, Sequence Alignment, 3T3 Cells, Sequence Deletion, Sequence Homology, Amino Acid, Mice, Knockout, Mice, Proto-Oncogene Proteins c-mdm2
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