Cited by 334Cancer-related Molecular PathwaysHeat shock proteins researchCell death mechanisms and regulation

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 access

Zeng, Xiaoya, Chen, Lihong, Jost, Christine A., Maya, Ruth, Keller, David, Wang, Xinjiang, Kaelin, William G., Oren, Moshe, Chen, Jiandong, Lu, Hua·1999·Molecular and Cellular Biology

DOI 10.1128/mcb.19.5.3257PMC PMC84120

Open this paper in CoChat — free account

Abstract

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.

Integrity signals

Registry

Crossref · 10.1128/mcb.19.5.3257

Cites

64 of 64 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

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-citation
Tumor 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).”
BackgroundResultInfluential
The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation
Momand, 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
p63, a p53 Homolog at 3q27–29, Encodes Multiple Products with Transactivating, Death-Inducing, and Dominant-Negative Activities
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

Show all 65 references

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.

Sorted by citations

CBP/p300 in cell growth, transformation, and development
Goodman, R. H., & Smolik, S. (2000) · Genes & Development · doi:10.1101/gad.14.13.1553 · Cited by 1,778
Themes and variations on ubiquitylation
Weissman, A. M. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35056563 · Cited by 1,507
The Pezcoller lecture: cancer cell cycles revisited.
Sherr, C. J. (2000) · PubMed · Cited by 1,193
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
Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis
Eischen, C. M., Weber, J. D., Roussel, M. F., Sherr, C. J., & Cleveland, J. L. (1999) · Genes & Development · doi:10.1101/gad.13.20.2658 · Cited by 819
Inhibiting the p53–MDM2 interaction: an important target for cancer therapy
Chène, P. (2003) · Nature Reviews Cancer · doi:10.1038/nrc991 · Cited by 765
The ARF/p53 pathway.
Sherr, C. J., & Weber, J. D. (2000) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)00038-6 · Cited by 654
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
The p53/p63/p73 family of transcription factors: overlapping and distinct functions
Levrero, M., Laurenzi, V. D., Costanzo, A., Sabatini, S., Gong, J., Wang, J. Y. J., & Melino, G. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.10.1661 · Cited by 567
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: p53 mimics, menaces and more
Yang, A., & McKeon, F. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35043127 · Cited by 506
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
DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis
Dasika, G. K., Lin, S.-C. J., Zhao, S., Sung, P., Tomkinson, A., & Lee, E. Y.-H. P. (1999) · Oncogene · doi:10.1038/sj.onc.1203283 · Cited by 427
Physical Interaction with Yes-associated Protein Enhances p73 Transcriptional Activity
Strano, S., Munarriz, E. R., Rossi, M., Castagnoli, L., Shaul, Y., Sacchi, A., Oren, M., Sudol, M., Cesareni, G., & Blandino, G. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010484200 · Cited by 418
Self-citation
Regulation of p53 stability
Ashcroft, M. A., & Vousden, K. H. (1999) · Oncogene · doi:10.1038/sj.onc.1203012 · Cited by 411
MDM2, an introduction.
Iwakuma, T., & Lozano, G. (2003) · PubMed · Cited by 390
p73 Induces apoptosis via PUMA transactivation and Bax mitochondrial translocation
Melino, G., Bernassola, F., Ranalli, M., Yee, K., Zong, W. X., Corazzari, M., Knight, R. A., Green, D. R., Thompson, C., & Vousden, K. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307469200 · Cited by 368
p53-independent functions of the p19ARF tumor suppressorPreprint
Weber, J. D., Jeffers, J. R., Rehg, J. E., Randle, D. H., Lozano, G., Roussel, M. F., Sherr, C. J., & Zambetti, G. P. (2000) · Genes & Development · doi:10.1101/gad.827300 · Cited by 361
Regulation of p53 Function
Woods, D. B., & Vousden, K. H. (2001) · Experimental Cell Research · doi:10.1006/excr.2000.5141 · Cited by 323
Activation and activities of the p53 tumour suppressor protein
Bálint, É., & Vousden, K. H. (2001) · British Journal of Cancer · doi:10.1054/bjoc.2001.2128 · Cited by 315
The ubiquitin–protein ligase Itch regulates p73 stability
Rossi, M., Laurenzi, V. D., Munarriz, E. R., Green, D. R., Liu, Y., Vousden, K. H., Cesareni, G., & Melino, G. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600444 · Cited by 303
The common and distinct target genes of the p53 family transcription factors
Harms, K. L., Nozell, S. E., & Chen, X. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3304-4 · Cited by 303
Cooperative Signals Governing ARF-Mdm2 Interaction and Nucleolar Localization of the Complex
Weber, J. D., Kuo, M.-L., Bothner, B. B., DiGiammarino, E. L., Kriwacki, R. W., Roussel, M. F., & Sherr, C. J. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.7.2517-2528.2000 · Cited by 275
MDM2 and Human Malignancies: Expression, Clinical Pathology, Prognostic Markers, and Implications for Chemotherapy
Rayburn, E., Zhang, R., He, J., & Wang, H. (2005) · Current Cancer Drug Targets · doi:10.2174/1568009053332636 · Cited by 265
p300/CBP/p53 interaction and regulation of the p53 response
Grossman, S. R. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.02226.x · Cited by 275
Polo-like Kinase 1 (Plk1) Inhibits p53 Function by Physical Interaction and Phosphorylation
Ando, K., Ozaki, T., Yamamoto, H., Furuya, K., Hosoda, M., Hayashi, S., Fukuzawa, M., & Nakagawara, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m314182200 · Cited by 262
p63 and p73 in human cancer: defining the network
DeYoung, M. P., & Ellisen, L. W. (2007) · Oncogene · doi:10.1038/sj.onc.1210337 · Cited by 261
Physical and Functional Interaction between p53 Mutants and Different Isoforms of p73
Strano, S., Munarriz, E. R., Rossi, M., Cristofanelli, B., Shaul, Y., Castagnoli, L., Levine, A. J., Sacchi, A., Cesareni, G., Oren, M., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003360200 · Cited by 241
Self-citation
C-Terminal Ubiquitination of p53 Contributes to Nuclear Export
Lohrum, M. A. E., Woods, D. B., Ludwig, R. L., Bálint, É., & Vousden, K. H. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.24.8521-8532.2001 · Cited by 237
p53 family update: p73 and p63 develop their own identities.
Irwin, M. S., & Kaelin, W. G. (2001) · PubMed · Cited by 222
Self-citation
p53-family proteins and their regulators: hubs and spokes in tumor suppression
Collavin, L., Lunardi, A., & Sal, G. D. (2010) · Cell Death and Differentiation · doi:10.1038/cdd.2010.35 · Cited by 225
Cyclin G Recruits PP2A to Dephosphorylate Mdm2
Okamoto, K., Li, H., Jensen, M. R., Zhang, T., Taya, Y., Thorgeirsson, S. S., & Prives, C. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00504-x · Cited by 215
Cooperative regulation of p53 by modulation of ternary complex formation with CBP/p300 and HDM2
Ferreon, J. C., Lee, C. W., Arai, M., Martinez-Yamout, M. A., Dyson, H. J., & Wright, P. E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0811023106 · Cited by 210
MDM2 promotes p21waf1/cip1 proteasomal turnover independently of ubiquitylation
Jin, Y., Lee, H., Zeng, S. X., Dai, M., & Lu, H. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg600 · Cited by 206
Self-citation
TP53 family members and human cancers
Bénard, J., Douc‐Rasy, S., & Ahomadegbe, J. (2003) · Human Mutation · doi:10.1002/humu.10172 · Cited by 215
A C-Terminal Inhibitory Domain Controls the Activity of p63 by an Intramolecular Mechanism
Serber, Z., Lai, H. C., Yang, A., Ou, H. D., Sigal, M. S., Kelly, A. E., Darimont, B. D., Duijf, P. H. G., van Bokhoven, H., McKeon, F., et al. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.24.8601-8611.2002 · Cited by 205
MDM2 inhibits p300-mediated p53 acetylation and activation by forming a ternary complex with the two proteins
Kobet, E., Zeng, X., Zhu, Y., Keller, D., & Lu, H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.23.12547 · Cited by 193
Self-citation
Mdm2: The Ups and Downs
Juven‐Gershon, T., & Oren, M. (1999) · Molecular Medicine · doi:10.1007/bf03402141 · Cited by 193
Self-citation
HDM2 antagonist Nutlin-3 disrupts p73-HDM2 binding and enhances p73 function
Lau, L. M. S., Nugent, J. K., Zhao, X., & Irwin, M. S. (2008) · Oncogene · doi:10.1038/sj.onc.1210707 · Cited by 182
HMGB1 and HMGB2 Cell-specifically Down-regulate the p53- and p73-dependent Sequence-specific Transactivation from the Human Bax Gene Promoter
Štros, M., Ozaki, T., Bačı́ková, A., Kageyama, H., & Nakagawara, A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110233200 · Cited by 182
Regulating the p53 system through ubiquitination
Yang, Y., Li, C.-C. H., & Weissman, A. M. (2004) · Oncogene · doi:10.1038/sj.onc.1207411 · Cited by 184
Control of p53 ubiquitination and nuclear export by MDM2 and ARF.
Zhang, Y., & Xiong, Y. (2001) · PubMed · Cited by 176
Autoinhibitory Regulation of p73 by ΔNp73 To Modulate Cell Survival and Death through a p73-Specific Target Element within the ΔNp73 Promoter
Nakagawa, T., Takahashi, M., Ozaki, T., Watanabe, K., Todo, S., Mizuguchi, H., Hayakawa, T., & Nakagawara, A. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.8.2575-2585.2002 · Cited by 177
The p53 gene family
Kaelin, W. G. (1999) · Oncogene · doi:10.1038/sj.onc.1202955 · Cited by 172
Self-citation
Mouse double minute antagonist Nutlin-3a enhances chemotherapy-induced apoptosis in cancer cells with mutant p53 by activating E2F1
Ambrosini, G., Sambol, E. B., Carvajal, D., Vassilev, L. T., Singer, S., & Schwartz, G. K. (2007) · Oncogene · doi:10.1038/sj.onc.1210136 · Cited by 163
Role of p73 in malignancy: tumor suppressor or oncogene?
Stiewe, T., & Pützer, B. M. (2002) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400995 · Cited by 156
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. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-0792 · Cited by 154
Targeting MDM2-p53 Interaction for Cancer Therapy: Are We There Yet?
Nag, S. A., Zhang, X., Srivenugopal, K. S., Wang, M.-H., Wang, W., & Zhang, R. (2014) · Current Medicinal Chemistry · doi:10.2174/09298673113206660325 · Cited by 156
E2F-1 induced apoptosis
Phillips, A. C., & Vousden, K. H. (2001) · APOPTOSIS · doi:10.1023/a:1011332625740 · Cited by 144
Stabilization of p53 by CP-31398 Inhibits Ubiquitination without Altering Phosphorylation at Serine 15 or 20 or MDM2 Binding
Wang, W., Takimoto, R., Rastinejad, F., & El‐Deiry, W. S. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.6.2171-2181.2003 · Cited by 144
p63 steps into the limelight: crucial roles in the suppression of tumorigenesis and metastasis
Su, X., Chakravarti, D., & Flores, E. R. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3446 · Cited by 143
Oncogenes Induce and Activate Endogenous p73 Protein
Zaika, A. I., Irwin, M. S., Sansome, C., & Moll, U. M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m005737200 · Cited by 138
How theTP53Family ProteinsTP63andTP73Contribute to Tumorigenesis: Regulators and Effectors
Candi, E., Agostini, M., Melino, G., & Bernassola, F. (2014) · Human Mutation · doi:10.1002/humu.22523 · Cited by 137
p73, a sophisticated p53 family member in the cancer world
Ozaki, T., & Nakagawara, A. (2005) · Cancer Science · doi:10.1111/j.1349-7006.2005.00116.x · Cited by 141
MDM2 and MDMX bind and stabilize the p53-related protein p73
Ongkeko, W. M., Wang, X. Q., Siu, W. Y., Lau, A. W. S., Yamashita, K., Harris, A. L., Cox, L. S., & Poon, R. Y. C. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80367-4 · Cited by 132
Self-citation
Evolution of Functions within the p53/p63/p73 Family
Laurenzi, V. D., & Melino, G. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb05602.x · Cited by 130
Targeted MDM2 Degradation Reveals a New Vulnerability for p53-Inactivated Triple-Negative Breast Cancer
Adams, C. M., Mitra, R., Xiao, Y., Michener, P., Palazzo, J., Chao, A., Gour, J., Cassel, J. A., Salvino, J. M., & Eischen, C. M. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-1131 · Cited by 126
Structure, function and regulation of p63 and p73
Levrero, M., Laurenzi, V. D., Costanzo, A., Gong, J., Melino, G., & Wang, J. Y. J. (1999) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400624 · Cited by 123
Regulation and function of the p53-related proteins: same family, different rules
Lohrum, M. A. E., & Vousden, K. H. (2000) · Trends in Cell Biology · doi:10.1016/s0962-8924(00)01736-0 · Cited by 122
Mdm2-mediated NEDD8 Modification of TAp73 Regulates Its Transactivation Function
Watson, I. R., Blanch, A., Lin, D. C. C., Ohh, M., & Irwin, M. S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m603654200 · Cited by 120
p53, p63 and p73 – solos, alliances and feuds among family members
Moll, U. M., Erster, S. H., & Zaika, A. (2001) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(01)00036-1 · Cited by 114
Structure and function in the p53 family
Arrowsmith, C. H. (1999) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400619 · Cited by 114
14‐3‐3γ binds to MDMX that is phosphorylated by UV‐activated Chk1, resulting in p53 activation
Jin, Y., Dai, M., Lu, S. Z., Xu, Y., Luo, Z., Zhao, Y., & Lu, H. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601010 · Cited by 116
Self-citation
Functional interplay between MDM2, p63/p73 and mutant p53
Stindt, M., Muller, P. A. J., Ludwig, R., Kehrloesser, S., Dötsch, V., & Vousden, K. H. (2014) · Oncogene · doi:10.1038/onc.2014.359 · Cited by 114
Targeting the p53-MDM2 pathway for neuroblastoma therapy: Rays of hope
Zafar, A., Wang, W., Liu, G., Xian, W., McKeon, F., Zhou, J., & Zhang, R. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.09.023 · Cited by 108
AMP-Activated Protein Kinase Induces p53 by Phosphorylating MDMX and Inhibiting Its Activity
He, G., Zhang, Y.-W., Lee, J., Zeng, S. X., Wang, Y. V., Luo, Z., Dong, X. C., Viollet, B., Wahl, G. M., & Lu, H. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.00670-13 · Cited by 107
Self-citation
TAp73 opposes tumor angiogenesis by promoting hypoxia-inducible factor 1α degradation
Amelio, I., Inoue, S., Markert, E. K., Levine, A. J., Knight, R. A., Mak, T. W., & Melino, G. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1410609111 · Cited by 106
A novel HECT-type E3 ubiquitin ligase, NEDL2, stabilizes p73 and enhances its transcriptional activity
Miyazaki, K., Ozaki, T., Kato, C., Hanamoto, T., Fujita, T., Irino, S., Watanabe, K., Nakagawa, T., & Nakagawara, A. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01347-0 · Cited by 103
MDM2’s social network
Fåhræus, R., & Olivares‐Illana, V. (2013) · Oncogene · doi:10.1038/onc.2013.410 · Cited by 103
Cell cycle regulatory functions of the human oncoprotein MDM2.
Deb, S. P. (2003) · PubMed · Cited by 96
The N-Terminal Domain of p73 Interacts with the CH1 Domain of p300/CREB Binding Protein and Mediates Transcriptional Activation and Apoptosis
Zeng, X., Li, X., Miller, A., Yuan, Z.-M., Yuan, W., Kwok, R. P. S., Goodman, R. H., & Lu, H. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.4.1299-1310.2000 · Cited by 97
Self-citation
MDM2 and MDMX can interact differently with ARF and members of the p53 family
Wang, X., Arooz, T., Siu, W. Y., Chiu, C. H. S., Lau, A., Yamashita, K., & Poon, R. Y. C. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02124-x · Cited by 94
Self-citation
The Human MDM2 Oncoprotein Increases the Transcriptional Activity and the Protein Level of the p53 Homolog p63
Calabrò, V., Mansueto, G., Parisi, T., Vivo, M., Calogero, R., & Mantia, G. L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107173200 · Cited by 94
Regulation and activation of p53 and its family members
Lohrum, M. A. E., & Vousden, K. H. (1999) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4400625 · Cited by 91
SSRP1 functions as a co‐activator of the transcriptional activator p63
Zeng, S. X., Dai, M., Keller, D. M., & Lu, H. (2002) · The EMBO Journal · doi:10.1093/emboj/cdf540 · Cited by 89
Self-citation
Expression of homologues for p53 and p73 in the softshell clam (Mya arenaria), a naturally-occurring model for human cancer
Kelley, M. L., Winge, P., Heaney, J. D., Stephens, R. E., Farrell, J. H., Beneden, R. J. V., Reinisch, C. L., Lesser, M. P., & Walker, C. W. (2001) · Oncogene · doi:10.1038/sj.onc.1204144 · Cited by 89
A New Twist in the Feedback Loop: Stress-Activated MDM2 Destabilization is Required for p53 Activation
Stommel, J. M., & Wahl, G. M. (2005) · Cell Cycle · doi:10.4161/cc.4.3.1522 · Cited by 90
From p63 to p53 across p73
Strano, S., Rossi, M., Fontemaggi, G., Munarriz, E. R., Soddu, S., Sacchi, A., & Blandino, G. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02119-6 · Cited by 87
MDM2 Inhibits PCAF (p300/CREB-binding Protein-associated Factor)-mediated p53 Acetylation
Jin, Y., Zeng, S. X., Dai, M., Yang, X., & Lu, H. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204078200 · Cited by 86
Self-citation
Modulation of p53 and p73 levels by cyclin G: implication of a negative feedback regulation
Ohtsuka, T., Ryu, H., Minamishima, Y. A., Ryo, A., & Lee, S. W. (2003) · Oncogene · doi:10.1038/sj.onc.1206306 · Cited by 84
MDMX (MDM4), a Promising Target for p53 Reactivation Therapy and BeyondPreprint
Marine, J., & Jochemsen, A. G. (2016) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a026237 · Cited by 82
MDMX Promotes Proteasomal Turnover of p21 at G1 and Early S Phases Independently of, but in Cooperation with, MDM2
Jin, Y., Zeng, S. X., Sun, X., Lee, H., Blattner, C., Xiao, Z. J., & Lu, H. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01198-07 · Cited by 79
Self-citation
Deletion of the COOH-terminal region of p73alpha enhances both its transactivation function and DNA-binding activity but inhibits induction of apoptosis in mammalian cells.
Ozaki, T., Naka, M., Takada, N., Tada, M., Sakiyama, S., & Nakagawara, A. (1999) · PubMed · Cited by 78
Ubiquitin and Ubiquitin-Like Modifications of the p53 Family
Watson, I. R., & Irwin, M. S. (2006) · Neoplasia · doi:10.1593/neo.06439 · Cited by 77
c-Jun Regulates the Stability and Activity of the p53 Homologue, p73
Toh, W. H., Siddique, M. M., Boominathan, L., Lin, K. W., & Sabapathy, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407672200 · Cited by 75
Comparative Analysis of P73 and P53 Regulation and Effector Functions
Li, F., Lee, S. W., & Aaronson, S. A. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.4.823 · Cited by 75
The p38MAPK Inhibitor SB203580 Alleviates Ultraviolet-Induced Phosphorylation at Serine 389 but Not Serine 15 and Activation of p53
Keller, D., Zeng, X., Li, X., Kapoor, M., Iordanov, M. S., Taya, Y., Lozano, G., Magun, B. E., & Lu, H. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1023 · Cited by 75
Self-citation
The p53 tumor suppressor: Critical regulator of life & death in cancer
Fisher, D. E. (2001) · APOPTOSIS · doi:10.1023/a:1009659708549 · Cited by 74
Regulation of p63 Function by Mdm2 and MdmX
Kadakia, M., Slader, C., & Berberich, S. J. (2001) · DNA and Cell Biology · doi:10.1089/10445490152122433 · Cited by 73
Protein stability and function of p73 are modulated by a physical interaction with RanBPM in mammalian cultured cells
Kramer, S., Ozaki, T., Miyazaki, K., Kato, C., Hanamoto, T., & Nakagawara, A. (2004) · Oncogene · doi:10.1038/sj.onc.1208257 · Cited by 73
Physical Interaction of p73 with c-Myc and MM1, a c-Myc-binding Protein, and Modulation of the p73 Function
Watanabe, K., Ozaki, T., Nakagawa, T., Miyazaki, K., Takahashi, M., Hosoda, M., Hayashi, S., Todo, S., & Nakagawara, A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111281200 · Cited by 71
Regulation of the p53 Family Proteins by the Ubiquitin Proteasomal Pathway
Bang, S., Kaur, S., & Kurokawa, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010261 · Cited by 69
Melatonin induces the apoptosis and inhibits the proliferation of human gastric cancer cells via blockade of the AKT/MDM2 pathway
Song, J., Ma, S., Luo, J., Zhang, H., Wang, R.-X., Liu, H., Li, L., Zhang, Z., & Zhou, R. (2018) · Oncology Reports · doi:10.3892/or.2018.6282 · Cited by 72
Small Molecule Antagonists of the MDM2 Oncoprotein as Anticancer Agents
Buolamwini, J. K., Addo, J. K., Kamath, S., Patil, S. A., Mason, M., & Ores, M. (2005) · Current Cancer Drug Targets · doi:10.2174/1568009053332672 · Cited by 69
p63 and p73: old members of a new family
Marín, M. C., & Kaelin, W. G. (2000) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/s0304-419x(00)00010-x · Cited by 67
Self-citation
The p53 family: same response, different signals?
Chen, X. (1999) · Molecular Medicine Today · doi:10.1016/s1357-4310(99)01545-2 · Cited by 67
Regulation of the p73 protein stability and degradation
Oberst, A., Rossi, M., Salomoni, P., Pandolfi, P. P., Oren, M., Melino, G., & Bernassola, F. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.03.158 · Cited by 66
Self-citation
Analysis of p73 in human borderline and invasive ovarian tumor
Ng, S.-W., Yiu, G. K., Liu, Y., Huang, L., Palnati, M., Jun, S. H., Berkowitz, R. S., & Mok, S. C. (2000) · Oncogene · doi:10.1038/sj.onc.1203512 · Cited by 66
Murine double minute 2: p53-independent roads lead to genome instability or death
Bouska, A. C., & Eischen, C. M. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.02.006 · Cited by 68
Interaction of regulators Mdm2 and Mdmx with transcription factors p53, p63 and p73
Zdzalik, M., Pustelny, K., Kędracka–Krok, S., Huben, K., Pęcak, A., Władyka, B., Jankowski, S., Dubin, A., Potempa, J., & Dubin, G. (2010) · Cell Cycle · doi:10.4161/cc.9.22.13871 · Cited by 65

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)
ORCID: Chen, Lihong
Maya, Ruth
Wang, Xinjiang
Kaelin, William G.
Oren, Moshe
Chen, Jiandong
Lu, Hua
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
DOI: 10.1128/mcb.19.5.3257
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
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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

MDM2 Suppresses p73 Function without Promoting p73 Degradation

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks