The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Mdm2 promotes the rapid degradation of p53
Abstract
The p53 tumour-suppressor protein exerts antiproliferative effects, including growth arrest and apoptosis, in response to various types of stress. The activity of p53 is abrogated by mutations that occur frequently in tumours, as well as by several viral and cellular proteins. The Mdm2 oncoprotein is a potent inhibitor of p53. Mdm2 binds the transcriptional activation domain of p53 and blocks its ability to regulate target genes and to exert antiproliferative effects. On the other hand, p53 activates the expression of the mdm2 gene in an autoregulatory feedback loop. The interval between p53 activation and consequent Mdm2 accumulation defines a time window during which p53 exerts its effects. We now report that Mdm2 also promotes the rapid degradation of p53 under conditions in which p53 is otherwise stabilized. This effect of Mdm2 requires binding of p53; moreover, a small domain of p53, encompassing the Mdm2-binding site, confers Mdm2-dependent detstabilization upon heterologous proteins. Raised amounts of Mdm2 strongly repress mutant p53 accumulation in tumour-derived cells. During recovery from DNA damage, maximal Mdm2 induction coincides with rapid p53 loss. We propose that the Mdm2-promoted degradation of p53 provides a new mechanism to ensure effective termination of the p53 signal.
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In the citing paper
“The best known feedback loop uses MDM2, a p53 target gene that encodes a ubiquitin ligase, which mediates degradation of p53.14, 15, 217”
From Census and evaluation of p53 target genes (2017) · cites this paper as [217]
In the citing paper
“In undamaged cells, p53 protein levels are maintained at minimal levels due to prompt proteasome-targeting polyubiquitination by the Mdm2 E3 ubiquitin ligase (Haupt et al., 1997; Honda et al., 1997; Kubbutat et al., 1997).”
From USP7 Is a Master Regulator of Genome Stability (2020) · cites this paper as Haupt et al., 1997
In the citing paper
“Mdm2 is a E3 ubiquitin ligase that targets p53 for degradation by the proteasome (7)”
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 [7]
In the citing paper
“Cellular proteins such as Mdm2 (MIM#164785) and Mdm4 (MIM#602704) can dampen p53 activity and allow the cell to live and propagate.”
From The Mdm network and its regulation of p53 activities: a rheostat of cancer risk (2014) · cites this paper as Haupt, et al., 1997
In the citing paper
“Mdm2 is an E3 ubiquitin ligase that ubiquitylates and targets p53 for degradation (Haupt, et al., 1997; Honda, et al., 1997; Kubbutat, et al., 1997).”
From The Mdm network and its regulation of p53 activities: a rheostat of cancer risk (2014) · cites this paper as Haupt, et al., 1997
In the citing paper
“Upon cell stress, this interaction is disrupted leading to increased levels of active, nuclear-localized p53.”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [64]
In the citing paper
“However, MDM2 is one of the most upregulated E3 ligases in cancer, leading to constant removal of p53 [63–65].”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [64]
In the citing paper
“MDM2 binds the p53 transactivation domain, leading to the inhibition of p53 function, nuclear export and degradation under physiological conditions.”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [64]
In the citing paper
“Mouse double minute 2 homolog (MDM2) is an oncoprotein with E3 ligase activity that targets the tumour suppressor p53 for ubiquitination.”
From Advances in targeted degradation of endogenous proteins (2019) · cites this paper as [64]
Citations
Cites
Participation of p53 protein in the cellular response to DNA damage.
Kastan, M. B., Onyekwere, O. C., Sidransky, D., Vogelstein, B., & Craig, R. W. (1991) · PubMed · Cited by 3,761
The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53
Scheffner, M., Huibregtse, J. M., Vierstra, R. D., & Howley, P. M. (1993) · Cell · doi:10.1016/0092-8674(93)90384-3 · Cited by 2,416
Palombella, V. J., Rando, O. J., Goldberg, A. L., & Maniatis, T. (1994) · Cell · doi:10.1016/s0092-8674(94)90482-0 · Cited by 2,089
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
Lin, J., Chen, J., Elenbaas, B., & Levine, A. J. (1994) · Genes & Development · doi:10.1101/gad.8.10.1235 · Cited by 652
In vivo ubiquitination and proteasome-mediated degradation of p53(1).
Maki, C. G., Huibregtse, J. M., & Howley, P. M. (1996) · PubMed · Cited by 645
Genetic and immunochemical analysis of mutant p53 in human breast cancer cell lines.
Bártek, J., Iggo, R. D., Gannon, J., & Lane, D. P. (1990) · PubMed · Cited by 603
Interaction between the retinoblastoma protein and the oncoprotein MDM2
Xiao, Z.-X., Chen, J., Levine, A. J., Modjtahedi, N., Xing, J. W., Sellers, W. R., & Livingston, D. M. (1995) · Nature · doi:10.1038/375694a0 · Cited by 586
p53 in growth control and neoplasia
Gottlieb, T. M., & Oren, M. (1996) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/0304-419x(95)00019-c · Cited by 483
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Hershko, A., & Ciechanover, A. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.425 · Cited by 8,840
Mechanisms Underlying Ubiquitination
Pickart, C. M. (2001) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.70.1.503 · Cited by 3,184
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
Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellular localization
Diehl, J. A., Cheng, M., Roussel, M. F., & Sherr, C. J. (1998) · Genes & Development · doi:10.1101/gad.12.22.3499 · Cited by 2,130
DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2
Shieh, S.-Y., Ikeda, M., Taya, Y., & Prives, C. (1997) · Cell · doi:10.1016/s0092-8674(00)80416-x · Cited by 2,100
Activation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53
Canman, C. E., Lim, D.-S., Cimprich, K. A., Taya, Y., Tamai, K., Sakaguchi, K., Appella, E., Kastan, M. B., & Siliciano, J. D. (1998) · Science · doi:10.1126/science.281.5383.1677 · Cited by 2,042
The first 30 years of p53: growing ever more complex.
Levine, A. J., & Oren, M. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2723 · Cited by 1,967
Self-citationKastenhuber, E. R., & Lowe, S. W. (2017) · Cell · doi:10.1016/j.cell.2017.08.028 · Cited by 1,906
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
Enhanced Phosphorylation of p53 by ATM in Response to DNA Damage
Banin, S., Moyal, L., Shieh, S.-Y., Taya, Y., Anderson, C. W., Chessa, L., Smorodinsky, N. I., Prives, C., Reiss, Y., Shiloh, Y., et al. (1998) · Science · doi:10.1126/science.281.5383.1674 · Cited by 1,797
Redox regulation of cell survival
Trachootham, D., Lu, W., Ogasawara, M. A., Valle, N. R.-D., & Huang, P. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2007.1957 · Cited by 1,781
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
Muller, P. A. J., & Vousden, K. H. (2013) · Nature Cell Biology · doi:10.1038/ncb2641 · Cited by 1,647
Kruse, J.-P., & Gu, W. (2009) · Cell · doi:10.1016/j.cell.2009.04.050 · Cited by 1,610
AMP-activated protein kinase induces a p53-dependent metabolic checkpoint
Jones, R. G., Plas, D. R., Kubek, S., Buzzai, M., Mu, J., Xu, Y., Birnbaum, M. J., & Thompson, C. B. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.03.027 · Cited by 1,619
Zhang, Y., Xiong, Y., & Yarbrough, W. G. (1998) · Cell · doi:10.1016/s0092-8674(00)81401-4 · Cited by 1,626
Pomerantz, J., Schreiber-Agus, N., Liégeois, N. J., Silverman, A., Alland, L., Chin, L., Potes, J., Chen, K., Orlow, I., Lee, H.-W., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81400-2 · Cited by 1,521
How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression
Aubrey, B. J., Kelly, G. L., Janic, A., Herold, M. J., & Strasser, A. (2018) · Cell Death & Differentiation · doi:10.1038/cdd.2017.169 · Cited by 1,395
Unravelling mechanisms of p53-mediated tumour suppression
Bieging-Rolett, K. T., Mello, S. S., & Attardi, L. D. (2014) · Nature reviews. Cancer · doi:10.1038/nrc3711 · Cited by 1,459
The complexity of p53 modulation: emerging patterns from divergent signalsPreprint
Giaccia, A. J., & Kastan, M. B. (1998) · Genes & Development · doi:10.1101/gad.12.19.2973 · Cited by 1,315
Bond, G. L., Hu, W., Bond, E. E., Robins, H., Lutzker, S. G., Arva, N. C., Bargonetti, J., Bartel, F., Taubert, H., Wuerl, P., et al. (2004) · Cell · doi:10.1016/j.cell.2004.11.022 · Cited by 1,265
Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization
Zindy, F., Eischen, C. M., Randle, D. H., Kamijo, T., Cleveland, J. L., Sherr, C. J., & Roussel, M. F. (1998) · Genes & Development · doi:10.1101/gad.12.15.2424 · Cited by 1,245
Mayo, L. D., & Donner, D. B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181181198 · Cited by 1,230
Malignant glioma: genetics and biology of a grave matterPreprint
Maher, E. A., Furnari, F. B., Bachoo, R. M., Rowitch, D. H., Louis, D. N., Cavenee, W. K., & DePinho, R. A. (2001) · Genes & Development · doi:10.1101/gad.891601 · Cited by 1,243
DNA damage activates p53 through a phosphorylation–acetylation cascade
Sakaguchi, K., Herrera, J. E., Saito, S., Miki, T., Bustin, M., Vassilev, A., Anderson, C. W., & Appella, E. (1998) · Genes & Development · doi:10.1101/gad.12.18.2831 · Cited by 1,204
The proteasome: a suitable antineoplastic target
Adams, J. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1361 · Cited by 1,214
The Pezcoller lecture: cancer cell cycles revisited.
Sherr, C. J. (2000) · PubMed · Cited by 1,193
The multiple mechanisms that regulate p53 activity and cell fate
Hafner, A., Bulyk, M. L., Jambhekar, A., & Lahav, G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0110-x · Cited by 1,129
Stott, F. J., Bates, S., James, M. C., McConnell, B. B., Starborg, M., Brookes, S., Palmero, I., Ryan, K. M., Hara, E., Vousden, K. H., et al. (1998) · The EMBO Journal · doi:10.1093/emboj/17.17.5001 · Cited by 1,178
The Rb/E2F pathway: expanding roles and emerging paradigms
Harbour, J. W., & Dean, D. C. (2000) · Genes & Development · doi:10.1101/gad.813200 · Cited by 1,153
When mutants gain new powers: News from the mutant p53 field
Brosh, R., & Rotter, V. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2693 · Cited by 1,132
Role of cell cycle in mediating sensitivity to radiotherapy
Pawlik, T. M., & Keyomarsi, K. (2004) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2004.03.005 · Cited by 1,155
Regulation of tumor angiogenesis by p53-induced degradation of hypoxia-inducible factor 1alpha.
Ravi, R. K., Mookerjee, B., Bhujwalla, Z. M., Sutter, T. R., Artemov, D., Zeng, Q., Dillehay, L. E., Madan, A., Semenza, G. L., & Bedi, A. (2000) · PubMed Central · Cited by 1,099
P53 in survival, death and metabolic health: a lifeguard with a licence to kill.
Kruiswijk, F., Labuschagne, C. F., & Vousden, K. H. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4007 · Cited by 1,080
Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL
Yosef, R., Pilpel, N., Tokarsky-Amiel, R., Biran, A., Ovadya, Y., Cohen, S., Vadai, E., Dassa, L., Shahar, E., Condiotti, R., et al. (2016) · Nature Communications · doi:10.1038/ncomms11190 · Cited by 1,032
A role for ATR in the DNA damage-induced phosphorylation of p53
Tibbetts, R. S., Brumbaugh, K. M., Williams, J. M., Sarkaria, J. N., Cliby, W. A., Shieh, S.-Y., Taya, Y., Prives, C., & Abraham, R. T. (1999) · Genes & Development · doi:10.1101/gad.13.2.152 · Cited by 1,046
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
Pathways of apoptotic and non-apoptotic death in tumour cells
Okada, H., & Mak, T. W. (2004) · Nature reviews. Cancer · doi:10.1038/nrc1412 · Cited by 1,066
Census and evaluation of p53 target genes
Fischer, M. (2017) · Oncogene · doi:10.1038/onc.2016.502 · Cited by 971
Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization
Li, M., Chen, D., Shiloh, A., Luo, J., Nikolaev, A. Y., Qin, J., & Gu, W. J. (2002) · Nature · doi:10.1038/nature737 · Cited by 1,048
The MDM2 gene amplification database
Momand, J. (1998) · Nucleic Acids Research · doi:10.1093/nar/26.15.3453 · Cited by 982
Regulation of p53 in response to DNA damage
Lakin, N. D., & Jackson, S. P. (1999) · Oncogene · doi:10.1038/sj.onc.1203015 · Cited by 987
p53 and Human Cancer: The First Ten Thousand Mutations
Hainaut, P. L., & Hollstein, M. C. (1999) · Advances in cancer research · doi:10.1016/s0065-230x(08)60785-x · Cited by 999
Mechanism and function of deubiquitinating enzymes
Amerik, A. Y., & Hochstrasser, M. (2004) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2004.10.003 · Cited by 1,010
Shieh, S.-Y., Ahn, J., Tamai, K., Taya, Y., & Prives, C. (2000) · Genes & Development · doi:10.1101/gad.14.3.289 · Cited by 972
Nucleolar Arf sequesters Mdm2 and activates p53
Weber, J. D., Taylor, L. J., Roussel, M. F., Sherr, C. J., & Bar-Sagi, D. (1999) · Nature Cell Biology · doi:10.1038/8991 · Cited by 940
p53 ubiquitination: Mdm2 and beyond
Brooks, C. L., & Gu, W. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.020 · Cited by 924
Nevins, J. R. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.7.699 · Cited by 939
Functional and physical interactions of the ARF tumor suppressor with p53 and Mdm2
Kamijo, T., Weber, J. D., Zambetti, G., Zindy, F., Roussel, M. F., & Sherr, C. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.14.8292 · Cited by 899
Rivlin, N., Brosh, R., Oren, M., & Rotter, V. (2011) · Genes & Cancer · doi:10.1177/1947601911408889 · Cited by 1,033
Self-citationThe DNA-dependent protein kinasePreprint
Smith, G. C. M., & Jackson, S. P. (1999) · Genes & Development · doi:10.1101/gad.13.8.916 · Cited by 903
Jiang, Y.-H., Armstrong, D., Albrecht, U., Atkins, C. M., Noebels, J. L., Eichele, G., Sweatt, J. D., & Beaudet, A. L. (1998) · Neuron · doi:10.1016/s0896-6273(00)80596-6 · Cited by 852
Hydrogen peroxide sensing, signaling and regulation of transcription factors
Marinho, H. S., Real, C., Cyrne, L., Soares, H., & Antunes, F. (2014) · Redox Biology · doi:10.1016/j.redox.2014.02.006 · Cited by 872
Takaoka, A., Hayakawa, S., Yanai, H., Stoiber, D., Negishi, H., Kikuchi, H., Sasaki, S., Imai, K., Shibue, T., Honda, K., et al. (2003) · Nature · doi:10.1038/nature01850 · Cited by 847
ROS and p53: A versatile partnership
Liu, B., Chen, Y., & Clair, D. K. S. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.01.011 · Cited by 842
DNA damage induces phosphorylation of the amino terminus of p53
Siliciano, J. D., Canman, C. E., Taya, Y., Sakaguchi, K., Appella, E., & Kastan, M. B. (1997) · Genes & Development · doi:10.1101/gad.11.24.3471 · Cited by 818
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
Mono- Versus Polyubiquitination: Differential Control of p53 Fate by Mdm2
Li, M., Brooks, C. L., Wu-Baer, F., Chen, D., Baer, R., & Gu, W. (2003) · Science · doi:10.1126/science.1091362 · Cited by 804
How the ubiquitin–proteasome system controls transcription
Muratani, M., & Tansey, W. P. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1049 · Cited by 814
Chk2/hCds1 functions as a DNA damage checkpoint in G1by stabilizing p53
Chehab, N. H., Malikzay, A., Appel, M., & Halazonetis, T. D. (2000) · Genes & Development · doi:10.1101/gad.14.3.278 · Cited by 805
Regulation ofp53downstream genes
El‐Deiry, W. S. (1998) · Seminars in Cancer Biology · doi:10.1006/scbi.1998.0097 · Cited by 805
Moll, U. M., & Petrenko, O. (2003) · PubMed · Cited by 778
The many substrates and functions of ATM.
Kastan, M. B., & Lim, D.-S. (2000) · Nature Reviews Molecular Cell Biology · doi:10.1038/35043058 · Cited by 779
Toward Maintaining the Genome: DNA Damage and Replication Checkpoints
Nyberg, K. A., Michelson, R. J., Putnam, C. W., & Weinert, T. A. (2002) · Annual Review of Genetics · doi:10.1146/annurev.genet.36.060402.113540 · Cited by 793
Induction of tumor apoptosis through a circular RNA enhancing Foxo3 activity
Du, W. W., Fang, L., Yang, W., Wu, N., Awan, F. M., Yang, Z., & Yang, B. B. (2016) · Cell Death and Differentiation · doi:10.1038/cdd.2016.133 · Cited by 776
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 p53–Mdm2 module and the ubiquitin system
Michael, D., & Oren, M. (2002) · Seminars in Cancer Biology · doi:10.1016/s1044-579x(02)00099-8 · Cited by 772
Self-citationTumor suppressor p53: Biology, signaling pathways, and therapeutic targeting
Borrero, L. J. H., & El‐Deiry, W. S. (2021) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2021.188556 · Cited by 805
Mutant p53 Gain-of-Function in CancerPreprint
Oren, M., & Rotter, V. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a001107 · Cited by 778
Self-citationStommel, J. M., Marchenko, N. D., Jimenez, G. S., Moll, U. M., Hope, T. J., & Wahl, G. M. (1999) · The EMBO Journal · doi:10.1093/emboj/18.6.1660 · Cited by 738
Role of p53 in Cell Death and Human Cancers
Ozaki, T., & Nakagawara, A. (2011) · Cancers · doi:10.3390/cancers3010994 · Cited by 650
Nsp3 of coronaviruses: Structures and functions of a large multi-domain protein
Lei, J., Kusov, Y., & Hilgenfeld, R. (2017) · Antiviral Research · doi:10.1016/j.antiviral.2017.11.001 · Cited by 734
Functional consequences of developmentally regulated alternative splicing
Kalsotra, A., & Cooper, T. A. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3052 · Cited by 729
Association of p19ARF with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53
Honda, R., & Yasuda, H. (1999) · The EMBO Journal · doi:10.1093/emboj/18.1.22 · Cited by 724
Agarwal, M. L., Taylor, W. R., Chernov, M. V., Chernova, O. B., & Stark, G. R. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.1.1 · Cited by 725
Pirh2, a p53-Induced Ubiquitin-Protein Ligase, Promotes p53 Degradation
Leng, R. P., Lin, Y., Ma, W., Wu, H., Lemmers, B., Chung, S., Parant, J. M., Lozano, G., Hakem, R., & Benchimol, S. (2003) · Cell · doi:10.1016/s0092-8674(03)00193-4 · Cited by 731
MEG3 noncoding RNA: a tumor suppressor
Zhou, Y., Zhang, X., & Klibanski, A. (2012) · Journal of Molecular Endocrinology · doi:10.1530/jme-12-0008 · Cited by 724
Tumor surveillance via the ARF–p53 pathwayPreprint
Sherr, C. J. (1998) · Genes & Development · doi:10.1101/gad.12.19.2984 · Cited by 718
ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage
Maya, R., Balass, M., Kim, S.-T., Shkedy, D., Leal, J.-F. M., Shifman, O., Moas, M., Buschmann, T., Ronai, Z., Shiloh, Y., et al. (2001) · Genes & Development · doi:10.1101/gad.886901 · Cited by 731
“cells was done as described previously (Haupt et al. 1997).”
BackgroundResultInfluentialSelf-citationBarlev, N. A., Liu, L., Chehab, N. H., Mansfield, K., Harris, K. G., Halazonetis, T. D., & Berger, S. L. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00414-2 · Cited by 710
Structure and physiological function of calpains
Sorimachi, H., Ishiura, S., & Suzuki, K. (1997) · Biochemical Journal · doi:10.1042/bj3280721 · Cited by 706
The ubiquitin ligase COP1 is a critical negative regulator of p53
Dornan, D., Wertz, I. E., Shimizu, H., Arnott, D. P., Frantz, G. D., Dowd, P., Rourke, K. O., Koeppen, H., & Dixit, V. M. (2004) · Nature · doi:10.1038/nature02514 · Cited by 700
A dynamic role of HAUSP in the p53-Mdm2 pathway
Li, M., Brooks, C. L., Kon, N., & Gu, W. (2004) · Molecular Cell · doi:10.1016/s1097-2765(04)00157-1 · Cited by 679
Chang, Y. S., Graves, B. J., Guerlavais, V., Tovar, C., Packman, K. E., To, K.-H., Olson, K. A., Kesavan, K. P., Gangurde, P., Mukherjee, A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1303002110 · Cited by 681
Oncogenic mutations of the p53 tumor suppressor: the demons of the guardian of the genome.
Sigal, A., & Rotter, V. (2000) · PubMed · Cited by 669
Regulation of p53 Translation and Induction after DNA Damage by Ribosomal Protein L26 and Nucleolin
Takagi, M., Absalon, M. J., McLure, K. G., & Kastan, M. B. (2005) · Cell · doi:10.1016/j.cell.2005.07.034 · Cited by 677
USP10 Regulates p53 Localization and Stability by Deubiquitinating p53
Yuan, J., Luo, K., Zhang, L., Cheville, J. C., & Lou, Z. (2010) · Cell · doi:10.1016/j.cell.2009.12.032 · Cited by 637
“Mdm2-mediated ubiquitination of p53 induces p53 nuclear export and degradation (Boyd et al., 2000; Freedman and Levine, 1998; Geyer et al., 2000; Haupt et al., 1997; Honda et al., 1997; Kubbutat and Vousden, 1997; Stommel et al., 1999).”
Twenty years of p53 research: structural and functional aspects of the p53 protein
May, P., & May, E. (1999) · Oncogene · doi:10.1038/sj.onc.1203285 · Cited by 682
Autophagy Inhibition Compromises Degradation of Ubiquitin-Proteasome Pathway Substrates
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Metadata
- Authors
- Haupt, Y., Maya, R., Kazaz, A., & Oren, M.
- Affiliations
- Hebrew University of Jerusalem (IL)
- Weizmann Institute of Science (IL)
- Venue
- Nature
- Published
- 1997-05
- Volume
- 387
- Issue
- 6630
- Pages
- 296-299
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2082979850
- Cited by
- 4,506
- References
- 29
- Citations by year
- 2026: 114 · 2025: 117 · 2024: 136 · 2023: 150 · 2022: 163 · 2021: 167 · 2020: 172 · 2019: 131 · 2018: 128 · 2017: 139 · 2016: 138 · 2015: 122 · 2014: 188 · 2013: 147 · 2012: 197
- FWCI
- 78.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- 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
- MDM2, p53, p53 degradation, protein stabilization, p53-MDM2 interaction, DNA damage response, tumour suppressor, autoregulatory loop, mutant p53
- MeSH terms
- Animals, HeLa Cells, Humans, Nuclear Proteins, Protein Binding, Proto-Oncogene Proteins, Recombinant Fusion Proteins, RNA, Messenger, Transfection, Tumor Cells, Cultured, Down-Regulation, Tumor Suppressor Protein p53, Mice, Proto-Oncogene Proteins c-mdm2
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