The DOI matches its Crossref record; 9 of the 9 references it cites were found in a registry or an index.
Synergistic activation of p53 by inhibition of MDM2 expression and DNA damage
Open accessAbstract
The MDM2 oncogene encodes an inhibitor of the p53 tumor suppressor protein that regulates p53 in a negative feedback loop. MDM2 gene amplification and overexpression occur in several types of tumors and are often associated with poor prognosis. An MDM2 antisense phosphorothioate oligodeoxynucleotide has been identified that effectively inhibits MDM2 expression in tumor cells containing MDM2 gene amplifications. Antisense inhibition of MDM2 is associated with a decrease in MDM2–p53 complex formation, increase in p53-inducible gene expression, increase in p53 transcriptional activity, and apoptosis. Significantly, inhibition of MDM2 expression enhances the activation of p53 by a DNA-damaging cancer chemotherapy agent in a synergistic fashion. Therefore, the MDM2 negative feedback pathway is an important limiting factor in DNA damage-induced p53 activation. MDM2 antisense oligonucleotides may be useful as antitumor agents alone or as enhancers of other conventional DNA-damaging drugs.
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Citations
Cites
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
Regulation of p53 stability by Mdm2
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Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53
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The mdm-2 oncogene can overcome wild-type p53 suppression of transformed cell growth.
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Cited by
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
The MDM2 gene amplification database
Momand, J. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.15.3453 · Cited by 982
MDM2 — master regulator of the p53 tumor suppressor protein
Momand, J., Wu, H.-H., & Dasgupta, G. (2000) · Gene · doi:10.1016/s0378-1119(99)00487-4 · Cited by 641
MDM2 inhibitors for cancer therapy
Vassilev, L. T. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2006.11.002 · Cited by 532
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
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Metadata
- Authors
- Chen, L., Agrawal, S., Zhou, W., Zhang, R., & Chen, J.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1998-01-06
- Volume
- 95
- Issue
- 1
- Pages
- 195-200
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2069060151
- Cited by
- 159
- References
- 9
- FWCI
- 7.03
- Type
- journal article
- Language
- en
- Open access
- green
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- Chen, L., Agrawal, S., Zhou, W., Zhang, R., & Chen, J. (1998). Synergistic activation of p53 by inhibition of MDM2 expression and DNA damage. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.95.1.195
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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