The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Efficient p53 Activation and Apoptosis by Simultaneous Disruption of Binding to MDM2 and MDMX
Abstract
The p53 tumor suppressor plays a key role in protection against malignant transformation. MDM2 and MDMX are important regulators of the transcriptional activity and stability of p53 by binding to its NH2 terminus. Recent studies suggest that inhibition of both MDM2 and MDMX is necessary for robust activation of p53 in certain tumor cells. However, small-molecule MDM2 inhibitors such as Nutlin fail to inhibit MDMX despite significant homology between the two proteins. The therapeutic efficacy of such compounds may be compromised by MDMX overexpression. To evaluate the feasibility and biological effects of simultaneously disrupting p53 binding to MDM2 and MDMX, we used phage display to identify a novel peptide that can inhibit p53 interactions with MDM2 (IC50 = 10 nmol/L) and MDMX (IC50 = 100 nmol/L). Expression of a scaffold protein (thioredoxin) displaying this peptide sequence by adenovirus disrupts both MDM2 and MDMX interaction with p53, resulting in efficient p53 activation, cell cycle arrest, and apoptosis of tumor cells overexpressing MDM2 and MDMX. Intratumoral injection of the adenovirus also induces growth suppression of tumor xenografts in mice in a p53-dependent fashion. These results show the therapeutic potential of targeting both MDM2 and MDMX in cancer, and provide a novel structural motif for the design of potent p53 activators. [Cancer Res 2007;67(18):8810–7]
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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
Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53
de Oca Luna, R. M., Wagner, D. S., & Lozano, G. (1995) · Nature · doi:10.1038/378203a0 · Cited by 1,420
Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53
Jones, S. N., Roe, A. E., Donehower, L. A., & Bradley, A. (1995) · Nature · doi:10.1038/378206a0 · Cited by 1,280
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
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 · cited 1×
“The MDM2 homologue MDMX also binds to p53 and inhibits p53-dependent transcription (5).”
BackgroundParant, J., Chavez-Reyes, A., Little, N. A., Yan, W., Reinke, V., Jochemsen, A. G., & Lozano, G. (2001) · Nature Genetics · doi:10.1038/ng714 · Cited by 517
Design of a synthetic Mdm2-binding mini protein that activates the p53 response in vivo
Böttger, A., Böttger, V., Sparks, A., Liu, W.-L., Howard, S. F., & Lane, D. P. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00374-5 · Cited by 363
HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53
Linares, L. K., Hengstermann, A., Ciechanover, A., Müller, S., & Scheffner, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2030930100 · Cited by 361
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
Cited by
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
Structural basis for high-affinity peptide inhibition of p53 interactions with MDM2 and MDMX
Pazgier, M., Liu, M., Zou, G., Yuan, W., Li, C., Li, C., Li, J., Monbo, J., Zella, D., Tarasov, S. G., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900947106 · Cited by 391
A Stapled p53 Helix Overcomes HDMX-Mediated Suppression of p53
Bernal, F., Wade, M., Godes, M., Davis, T. N., Whitehead, D. G., Kung, A. L., Wahl, G. M., & Walensky, L. D. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.10.024 · Cited by 285
Dual inhibition of MDMX and MDM2 as a therapeutic strategy in leukemia
Carvajal, L. A., Neriah, D. B., Senecal, A., Benard, L., Thiruthuvanathan, V., Yatsenko, T., Narayanagari, S.-R., Wheat, J. C., Todorova, T. I., Mitchell, K., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aao3003 · Cited by 249
Identification 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
Metadata
- Authors
- Hu, B., Gilkes, D. M., & Chen, J.
- Venue
- Cancer Research
- Published
- 2007-09-15
- Volume
- 67
- Issue
- 18
- Pages
- 8810-8817
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2100589388
- Cited by
- 213
- References
- 22
- FWCI
- 7.85
- Type
- journal article
- Language
- en
- Open access
- closed
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- Hu, B., Gilkes, D. M., & Chen, J. (2007). Efficient p53 Activation and Apoptosis by Simultaneous Disruption of Binding to MDM2 and MDMX. Cancer Research. https://doi.org/10.1158/0008-5472.can-07-1140
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