The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Inactivation of the p53-homologue p73 by the mdm2-oncoprotein
Abstract
The p73beta protein shares structural and functional similarities with the tumor suppressor gene product p53. Both proteins activate transcription from p53-responsive promoters. p53's activity is antagonized by the mdm2 protein (also termed hdm2 in human cells). Complex formation between p53 and mdm2 results in p53's transcriptional inactivation and destabilization. Here we show that overexpression of mdm2 reduces p73beta's ability to activate transcription, too. The mdm2 protein forms a specific complex with p73beta in vitro with an efficiency comparable to p53-binding. Further, both p73beta and p53 relocalize a transport-defective mutant of mdm2 from the cytoplasm to the nucleus, arguing that complex formation occurs in vivo as well. Mutational analysis suggests that the interaction between p73beta and mdm2 follows structural principles analogous to the p53-mdm2-complex. Whereas p53 is destabilized in the presence of mdm2, the amount of intracellular p73beta was not detectably reduced by mdm2. The carboxyterminal RING finger domain of mdm2 was found to be required to reduce the intracellular abundance of p53, but it was dispensable for transcriptionally inactivating either p53 or p73beta. Our results suggest that the autoregulatory feedback loop between p53 and mdm2 also controls p73's activity, but that mdm2-mediated protein degradation is unique to p53.
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“While p53 and p73α can both interact with Mdm2 in the same N-terminal hydrophobic pocket (12), Mdm2 does not ubiquitinate p73α (44–46).”
From Potentiation of carboplatin-mediated DNA damage by the Mdm2 modulator Nutlin-3a in a humanized orthotopic breast-to-lung metastatic model (2015) · cites this paper as [44]
Citations
Cites
p53, the cellular gatekeeper for growth and division
Levine, A. J. (1997) · Cell · doi:10.1016/s0092-8674(00)81871-1 · Cited by 7,693
Lane, D. P. (1992) · Nature · doi:10.1038/358015a0 · Cited by 5,138
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
Kubbutat, M. H. G., Jones, S. N., & Vousden, K. H. (1997) · Nature · doi:10.1038/387299a0 · Cited by 3,312 · cited 2×
“…(Figure 3e), further supporting the concept that the p73b interacts with mdm2 in vivo as well as in vitro. mdm2 does not detectably destabilize p73 In the presence of mdm2, p53 is rapidly degraded, leading to a reduced steady-state level of the protein (Haupt et al., 1997; Kubbutat et al., 1997).”
BackgroundMomand, J., Zambetti, G. P., Olson, D. C., George, D., & Levine, A. J. (1992) · Cell · doi:10.1016/0092-8674(92)90644-r · Cited by 3,113
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
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
Amplification of a gene encoding a p53-associated protein in human sarcomas
Oliner, J. D., Kinzler, K. W., Meltzer, P. S., George, D. L., & Vogelstein, B. (1992) · Nature · doi:10.1038/358080a0 · Cited by 1,949
The p53-mdm-2 autoregulatory feedback loop.
Wu, X., Bayle, J. H., Olson, D., & Levine, A. J. (1993) · Genes & Development · doi:10.1101/gad.7.7a.1126 · Cited by 1,801
Kaghad, M., Bonnet, H., Yang, A., Créancier, L., Biscan, J.-C., Valent, A., Minty, A. J., Chalon, P., Lélias, J.-M., Dumont, X., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80540-1 · Cited by 1,659
Research works printed but not linked: 2
- Chen J, Marechal V and Levine AJ. . 1993 Mol. Cell. Biol. 13: 4107–4114. · DOI
- Dobblestein M and Roth J. . 1997 J. Gen. Virol. in press.
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Themes and variations on ubiquitylation
Weissman, A. M. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056563 · Cited by 1,507
Mdm2 Is a RING Finger-dependent Ubiquitin Protein Ligase for Itself and p53
Fang, S., Jensen, J. P., Ludwig, R. L., Vousden, K. H., & Weissman, A. M. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.12.8945 · Cited by 1,044
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
p73: Friend or foe in tumorigenesis
Melino, G., Laurenzi, V. D., & Vousden, K. H. (2002) · Nature reviews. Cancer · doi:10.1038/nrc861 · Cited by 554
p63 and p73: Roles in Development and Tumor Formation
Moll, U. M., & Slade, N. (2004) · Molecular Cancer Research · doi:10.1158/1541-7786.371.2.7 · Cited by 488
Metadata
- Authors
- Dobbelstein, M., Wienzek, S., König, C., & Roth, J.
- Affiliations
- Philipps University of Marburg (DE)
- Venue
- Oncogene
- Published
- 1999-03-25
- Volume
- 18
- Issue
- 12
- Pages
- 2101-2106
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2312957642
- Cited by
- 161
- References
- 40
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 4 · 2015: 6 · 2014: 6 · 2013: 4 · 2012: 5
- FWCI
- 7.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncogene (publishedVersion)
- PubMed (publishedVersion)
- 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
- p53, MDM2, transcriptional inactivation, protein-protein interaction, RING domain, protein degradation, autoregulatory loop, tumor suppressor proteins, nuclear translocation
- MeSH terms
- Tumor Protein p73, Biological Transport, Cell Compartmentation, Cell Nucleus, Cytoplasm, DNA-Binding Proteins, Nuclear Proteins, Protein Binding, Proto-Oncogene Proteins, Transcription Factors, Transcriptional Activation, Genes, Tumor Suppressor, Tumor Suppressor Protein p53, Tumor Suppressor Proteins, Proto-Oncogene Proteins c-mdm2
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