The DOI matches its Crossref record; 64 of the 65 references it cites were found in a registry or an index.
MDM2 Suppresses p73 Function without Promoting p73 Degradation
Open accessAbstract
The newly identified p53 homolog p73 can mimic the transcriptional activation function of p53. We investigated whether p73, like p53, participates in an autoregulatory feedback loop with MDM2. p73 bound to MDM2 both in vivo and in vitro. Wild-type but not mutant MDM2, expressed in human p53 null osteosarcoma Saos-2 cells, inhibited p73- and p53-dependent transcription driven by the MDM2 promoter-derived p53RE motif as measured in transient-transfection and chloramphenicol acetyltransferase assays and also inhibited p73-induced apoptosis in p53-null human lung adenocarcinoma H1299 cells. MDM2 did not promote the degradation of p73 but instead disrupted the interaction of p73, but not of p53, with p300/CBP by competing with p73 for binding to the p300/CBP N terminus. Both p73alpha and p73beta stimulated the expression of the endogenous MDM2 protein. Hence, MDM2 is transcriptionally activated by p73 and, in turn, negatively regulates the function of this activator through a mechanism distinct from that used for p53 inactivation.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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
“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 [45]
In the citing paper
“Rather, Mdm2 sequesters p73α thereby preventing downstream p73α-mediated signaling (45).”
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 [45]
Citations
Cites
WAF1, a potential mediator of p53 tumor suppression
El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W., & Vogelstein, B. (1993) · Cell · doi:10.1016/0092-8674(93)90500-p · Cited by 8,321
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
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
Self-citationTumor suppressor p53 is a direct transcriptional activator of the human bax gene
Toshiyuki, M., & Reed, J. C. (1995) · Cell · doi:10.1016/0092-8674(95)90412-3 · Cited by 4,063
p21 is a universal inhibitor of cyclin kinases
Xiong, Y., Hannon, G., Zhang, H., Casso, D., Kobayashi, R., & Beach, D. (1993) · Nature · doi:10.1038/366701a0 · Cited by 3,691
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 5×
“MDM2 can also stimulate the ubiquitination (24) and proteolytic degradation of p53 (22, 31), although it is also proposed that MDM2 down-regulates p53 by concealing its transactivation domain (7, 8, 38).”
BackgroundResultInfluentialMomand, 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
A model for p53-induced apoptosis
Polyak, K., Xia, Y., Zweier, J. L., Kinzler, K. W., & Vogelstein, B. (1997) · Nature · doi:10.1038/38525 · Cited by 2,500
p53: puzzle and paradigm.Preprint
Ko, L. J., & Prives, C. L. (1996) · Genes & Development · doi:10.1101/gad.10.9.1054 · Cited by 2,346
Yang, A., Kaghad, M., Wang, Y., Gillett, E. S., Fleming, M. D., Dötsch, V., Andrews, N. C., Caput, D., & McKeon, F. (1998) · Molecular Cell · doi:10.1016/s1097-2765(00)80275-0 · Cited by 2,118
Research works printed but not linked: 3
- 10.1128/mcb.13.7.4107-4114.1993 · DOI
- 10.1128/mcb.13.1.301-306.1993 · DOI · Paper page
- Lu, H., J. Lin, J. Chen, and J. Levine 1996. Regulation of p53 transcriptional function: TAFs and MDM2. Harvey Lect. 90:81–93.
Cited by
Sorted by citations
Items 301–332 of 332
Roh, J.-L., & Koch, W. M. (2014) · Springer eBooks · doi:10.1007/978-1-4614-8815-6_12
On the structure-function relationship of p73
Nyman, U. (2009) · Figshare
Multiple modes of Mdmx regulation affect p53 activation
Gilkes, D. M. (2008) · Digital Commons - University of South Florida (University of South Florida)
p73 Affects Cell Fate and Tumorigenesis
Ramadan, S. M., Sayan, E., Oberst, A., Chikh, A., Pietroni, V., Rufini, A., Melino, G., & Bernassola, F. (2006) · Wiley eBooks · doi:10.1002/9783527619665.ch20
The Role of p53 and p73 Genes in Tumor Formation
(2005) · Handbook of immunohistochemistry and in situ hybridization of human carcinomas · doi:10.1016/s1874-5784(05)80016-9
Transcriptional regulation of cell life and death decisions by p73
Muppani, N. R. (2013) · Figshare
The effects of leptomycin B on HPV-infected cells
Jolly, C. (2008) · St Andrews Research Repository (St Andrews Research Repository)
Enge, M. (2009) · Figshare
The p53 homolog p63 modulates acute and chronic damage in irradiated salivary glands
Mitchell, G. C. (2010) · UA Campus Repository (The University of Arizona)
Pfeifer, D. (2009) · DiVA (Linkoping University)
Dynamical patterns of p53 states driven by PMLPreprint
Alam, M. J., Al-Shammari, E., & Singh, R. K. B. (2015) · arXiv (Cornell University) · doi:10.48550/arxiv.1504.05084
Phospho-regulation and metastatic potential of Murine Double Minute 2
Batuello, C. N. (2012) · doi:10.7912/c2/1866
Modulation of the Mdm2 signaling axis sensitizes triple-negative breast cancer cells to carboplatin
Tonsing-Carter, E. Y. (2014) · ProQuest Demo Repository · doi:10.7912/c2/308
IN VIVO SIGNIFICANCE OF THE MDM4 AND P73 INTERACTION DURING DEVELOPMENT AND TUMORIGENESIS
Tashakori, M. (2015) · Digital Commons-TMC (Texas Medical Center)
Characterization of the Ubiquitin/Nedd8 E3 ligase activity of the Mdm2/MdmX complex
Singh, R. K. (2007) · Kölner Universitäts PublikationsServer (Universität zu Köln)
Identification of novel and direct target genes of p73
Lapi, E. (2008) · Cineca Institutional Research Information System (Tor Vergata University)
Death Shapes Life: Characterizing the Role of p63 and p73 During Neural Development and Aging
Dugani, S. (2011) · TSpace (University of Toronto)
An Investigation of the Function of IκB Family Member Bcl-3 and its Role in Oncogenesis
Kashatus, D. F. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/jf96-hd10
Targeting MDM2, the antagonist of the tumor suppressor p53
Sriraman, A. (2018) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-7056
Data from Small-Molecule MDM2 Antagonists as a New Therapy Concept for Neuroblastoma
Maerken, T. V., Speleman, F., Vermeulen, J., Lambertz, I., Clercq, S. D., Smet, E. D., Yigit, N., Coppens, V., Philippé, J., Paepe, A. D., et al. (2023) · doi:10.1158/0008-5472.c.6494438
Data from Small-Molecule MDM2 Antagonists as a New Therapy Concept for Neuroblastoma
Maerken, T. V., Speleman, F., Vermeulen, J., Lambertz, I., Clercq, S. D., Smet, E. D., Yigit, N., Coppens, V., Philippé, J., Paepe, A. D., et al. (2023) · doi:10.1158/0008-5472.c.6494438.v1
Data from p73β-Mediated Apoptosis Requires p57kip2 Induction and IEX-1 Inhibition
González, S., Pérez‐Pérez, M. M., Hernando, E., Serrano, M., & Cordon‐Cardo, C. (2023) · doi:10.1158/0008-5472.c.6494121
Data from p73β-Mediated Apoptosis Requires p57kip2 Induction and IEX-1 Inhibition
González, S., Pérez‐Pérez, M. M., Hernando, E., Serrano, M., & Cordon‐Cardo, C. (2023) · doi:10.1158/0008-5472.c.6494121.v1
Punga, T. (2003) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Implication de la biogenèse des ribosomes dans la tumorigenèse
Belin, S. (2009) · theses.fr (ABES) · doi:10.70675/5dfbb9f9z6739z475az845azcd0a7cd6f91e
Expression et fonctions biologiques de l’isoforme ΔNp63
de Gasperis, A. (2011) · theses.fr (ABES) · doi:10.70675/3b754ccbz3f14z4949z9f45z1bdd5995d3d3
de Abreu, P. A. (2016) · theses.fr (ABES) · doi:10.70675/a49b7f77z1189z425fz86b8z8ee9f8fa327a
Zhang, Y., Xun, C., Shi, C., Wang, R., Gao, Y., Pan, D., Guo, Y., & Wei, L. (2026) · Journal of Advanced Research · doi:10.1016/j.jare.2026.04.019
BindingDB (2025) · UC San Diego · doi:10.7270/q2wq08f2
Metadata
- Authors
- Zeng, X., Chen, L., Jost, C. A., Maya, R., Keller, D., Wang, X., Kaelin, W. G., Oren, M., Chen, J., & Lu, H.
- Affiliations
- Oregon Health & Science University (US)
- Louisiana State University (US)
- Harvard University (US)
- Weizmann Institute of Science (IL)
- Howard Hughes Medical Institute (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1999-05
- Volume
- 19
- Issue
- 5
- Pages
- 3257-3266
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC84120
- OpenAlex
- W2106031335
- Cited by
- 334
- References
- 65
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 1 · 2023: 6 · 2022: 6 · 2021: 6 · 2020: 9 · 2019: 8 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 13 · 2014: 10 · 2013: 11 · 2012: 12
- FWCI
- 13.51
- 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 Cancer Institute (R01 CA 79721-01, R01CA079721)
- 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 › Cell death mechanisms and regulation
- Keywords
- MDM2, p73, p53, CBP/p300, transcriptional activation, autoregulatory loop, p53 response elements, apoptosis, protein-protein interaction, p73alpha, p53-null cells
- MeSH terms
- Tumor Protein p73, DNA-Binding Proteins, Feedback, Fluorescent Antibody Technique, Gene Expression Regulation, Humans, Mutation, Nuclear Proteins, Protein Binding, Proto-Oncogene Proteins, Recombinant Proteins, Transcription, Genetic, Tumor Cells, Cultured, Transcriptional Activation, Trans-Activators, Genes, Tumor Suppressor, Tumor Suppressor Protein p53, Apoptosis, Genes, Reporter, Tumor Suppressor Proteins, Proto-Oncogene Proteins c-mdm2
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
