Mdm2-mediated ubiquitylation: p53 and beyond

In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2

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Mdm2 promotes the rapid degradation of p53

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Regulation of p53 stability by Mdm2

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The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation

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Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas

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Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53

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Amplification of a gene encoding a p53-associated protein in human sarcomas

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Restoration of p53 function leads to tumour regression in vivo

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Recognition of the polyubiquitin proteolytic signal

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Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53

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Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53

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mdm2 expression is induced by wild type p53 activity.

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Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53

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A Single Nucleotide Polymorphism in the MDM2 Promoter Attenuates the p53 Tumor Suppressor Pathway and Accelerates Tumor Formation in Humans

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Regulation of Membrane Protein Transport by Ubiquitin and Ubiquitin-Binding Proteins

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Mdm2 Is a RING Finger-dependent Ubiquitin Protein Ligase for Itself and p53

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Dynamics of the p53-Mdm2 feedback loop in individual cells

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Nucleolar Arf sequesters Mdm2 and activates p53

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p53 ubiquitination: Mdm2 and beyond

Brooks, C. L., & Gu, W. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.020 · Cited by 924 · see citing works

Acetylation Is Indispensable for p53 Activation

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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 · see citing works

The p53–Mdm2 module and the ubiquitin system

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Small molecule RITA binds to p53, blocks p53–HDM-2 interaction and activates p53 function in tumors

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A leucine-rich nuclear export signal in the p53 tetramerization domain: regulation of subcellular localization and p53 activity by NES masking

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ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage

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ERK promotes tumorigenesis by inhibiting FOXO3a via MDM2-mediated degradation

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Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis

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The genetics of the p53 pathway, apoptosis and cancer therapy

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p53 polymorphisms: cancer implications

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Oscillations and variability in the p53 system

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The lore of the RINGs: substrate recognition and catalysis by ubiquitin ligases

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Modeling the Therapeutic Efficacy of p53 Restoration in Tumors

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Divorcing ARF and p53: an unsettled case

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Functions of the MDM2 oncoprotein

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Mdm2-Mediated NEDD8 Conjugation of p53 Inhibits Its Transcriptional Activity

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p53 Mutation and MDM2 amplification in human soft tissue sarcomas.

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Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner

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Untitled work

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Polyubiquitination of p53 by a Ubiquitin Ligase Activity of p300

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Yin Yang 1 Is a Negative Regulator of p53

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Recurrent Initiation: A Mechanism for Triggering p53 Pulses in Response to DNA Damage

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Nucleolar protein NPM interacts with HDM2 and protects tumor suppressor protein p53 from HDM2-mediated degradation

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MDM2, an introduction.

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Accelerated MDM2 auto‐degradation induced by DNA‐damage kinases is required for p53 activation

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Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis

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Multiple C-Terminal Lysine Residues Target p53 for Ubiquitin-Proteasome-Mediated Degradation

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NUMB controls p53 tumour suppressor activity

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Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase

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The inherent instability of mutant p53 is alleviated by Mdm2 or p16 INK4a lossPreprint

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Keeping p53 in check: essential and synergistic functions of Mdm2 and Mdm4

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PML regulates p53 stability by sequestering Mdm2 to the nucleolus

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Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells

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Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans

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The Wip1 Phosphatase Acts as a Gatekeeper in the p53-Mdm2 Autoregulatory Loop

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Posttranslational modification of MDM2.

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Cytoplasmic destruction of p53 by the endoplasmic reticulum‐resident ubiquitin ligase ‘Synoviolin’

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Repression of p53-mediated transcription by MDM2: a dual mechanism

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Mdm4 and Mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells <i>in vivo</i>

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Mdm2 is critically and continuously required to suppress lethal p53 activity in vivo

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The mdm-2 gene is induced in response to UV light in a p53-dependent manner.

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Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation

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C-Terminal Ubiquitination of p53 Contributes to Nuclear Export

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Targeted expression of MDM2 uncouples S phase from mitosis and inhibits mammary gland development independent of p53.

Lundgren, K., Montes de Oca Luna, R., McNeill, Y. B., Emerick, E. P., Spencer, B., Barfield, C. R., Lozano, G., Rosenberg, M. P., & Finlay, C. A. (1997) · Genes &amp; Development · doi:10.1101/gad.11.6.714 · Cited by 235 · see citing works

<i>mdm2</i> Is Critical for Inhibition of p53 during Lymphopoiesis and the Response to Ionizing Irradiation

Mendrysa, S. M., McElwee, M. K., Michalowski, J., O'Leary, K. A., Young, K. M., & Perry, M. E. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.2.462-473.2003 · Cited by 234 · see citing works

MDMX: from bench to bedside

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C-terminal modifications regulate MDM2 dissociation and nuclear export of p53

Carter, S., Bischof, O., Dejean, A., & Vousden, K. H. (2007) · Nature Cell Biology · doi:10.1038/ncb1562 · Cited by 225 · see citing works

Asymmetric cell division

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Mdm2-dependent ubiquitination and degradation of the insulin-like growth factor 1 receptor

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A Novel Cofactor for p300 that Regulates the p53 Response

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Impact of the MDM2 SNP309 and p53 Arg72Pro polymorphism on age of tumour onset in Li-Fraumeni syndrome

Bougeard, G., Baert-Desurmont, S., Tournier, I., Vasseur, S., Martin, C., Brugières, L., Chompret, A., Paillerets, B. B., Stoppa‐Lyonnet, D., Bonaïti‐Pellié, C., et al. (2005) · Journal of Medical Genetics · doi:10.1136/jmg.2005.037952 · Cited by 216 · see citing works

Tumor suppression and normal aging in mice with constitutively high p53 activity

Mendrysa, S. M., O'Leary, K. A., McElwee, M. K., Michalowski, J., Eisenman, R. N., Powell, D. A., & Perry, M. E. (2006) · Genes &amp; Development · doi:10.1101/gad.1378506 · Cited by 210 · see citing works

The RING domain of Mdm2 mediates histone ubiquitylation and transcriptional repression

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The Mdm2 RING domain C-terminus is required for supramolecular assembly and ubiquitin ligase activity

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A mouse p53 mutant lacking the proline-rich domain rescues Mdm4 deficiency and provides insight into the Mdm2-Mdm4-p53 regulatory network

Toledo, F., Krummel, K. A., Lee, C. J., Liu, C.-W., Rodewald, L.-W., Tang, M., & Wahl, G. M. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.03.014 · Cited by 199 · see citing works

Regulation of Mdm2-Directed Degradation by the C Terminus of p53

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Topors Functions as an E3 Ubiquitin Ligase with Specific E2 Enzymes and Ubiquitinates p53

Rajendra, R., Malegaonkar, D., Pungaliya, P., Marshall, H., Rasheed, Z. A., Brownell, J. E., Liu, L. F., Lutzker, S. G., Saleem, A., & Rubin, E. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.c400300200 · Cited by 192 · see citing works

The C-terminal lysines fine-tune p53 stress responses in a mouse model, but are not required for stability control or transactivation

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Mdmx as an essential regulator of p53 activity

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Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2

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MDM2-Regulated Degradation of HIPK2 Prevents p53Ser46 Phosphorylation and DNA Damage-Induced Apoptosis

Rinaldo, C., Prodosmo, A., Mancini, F., Iacovelli, S., Sacchi, A., Moretti, F., & Soddu, S. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.02.008 · Cited by 172 · see citing works

The MDM2 oncogene overexpression in chronic lymphocytic leukemia and low-grade lymphoma of B-cell origin

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An essential function of the extreme C-terminus of MDM2 can be provided by MDMX

Uldrijan, S., Pannekoek, W., & Vousden, K. H. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601469 · Cited by 170 · see citing works

Targeting Mdm2 and Mdmx in cancer therapy: better living through medicinal chemistry?

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Synergistic roles of Mdm2 and Mdm4 for p53 inhibition in central nervous system development

Xiong, S., Van Pelt, C. S., Elizondo-Fraire, A. C., Liu, G., & Lozano, G. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508500103 · Cited by 155 · see citing works

mdm2 and bax, downstream mediators of the p53 response, are degraded by the ubiquitin-proteasome pathway.

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Tissue-specific differences of p53 inhibition by Mdm2 and Mdm4

Grier, J. D., Xiong, S., Elizondo-Fraire, A. C., Parant, J. M., & Lozano, G. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.26.1.192-198.2006 · Cited by 149 · see citing works

Untitled work

(2003) · PubMed · Cited by 147 · see citing works

Cooperation between the ribosomal proteins L5 and L11 in the p53 pathway

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An alternatively spliced HDM2 product increases p53 activity by inhibiting HDM2

Evans, S. C., Viswanathan, M., Grier, J. D., Narayana, M., El‐Naggar, A. K., & Lozano, G. (2001) · Oncogene · doi:10.1038/sj.onc.1204533 · Cited by 138 · see citing works

The Mdm2 Oncoprotein Interacts with the Cell Fate Regulator Numb

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Hedgehog signaling overrides p53-mediated tumor suppression by activating Mdm2

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A Chromatin-associated and Transcriptionally Inactive p53-Mdm2 Complex Occurs in mdm2 SNP309 Homozygous Cells

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Critical Contribution of the MDM2 Acidic Domain to p53 Ubiquitination

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Critical Role for a Central Part of Mdm2 in the Ubiquitylation of p53

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Mdm2 Promotes Genetic Instability and Transformation Independent of p53

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The single-nucleotide polymorphism 309 in the MDM2 gene contributes to the Li–Fraumeni syndrome and related phenotypes

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RYBP stabilizes p53 by modulating MDM2

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CARPs Are Ubiquitin Ligases That Promote MDM2-independent p53 and Phospho-p53ser20 Degradation

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c-Fos Proto-Oncoprotein Is Degraded by the Proteasome Independently of Its Own Ubiquitinylation In Vivo

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Physical and Functional Interactions between PML and MDM2

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The Yeast and Mammalian Ras Pathways Control Transcription of Heat Shock Genes Independently of Heat Shock Transcription Factor

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Mdm2, but not Mdm4, protects terminally differentiated smooth muscle cells from p53-mediated caspase-3-independent cell death

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Unlocking the Mdm2-p53 loop: Ubiquitin is the key

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Expression of the wild-type p53 antioncogene induces guanine nucleotide-dependent stem cell division kinetics.

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Overexpression of the wip1 gene abrogates the p38 MAPK/p53/Wip1 pathway and silences p16 expression in human breast cancers

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Putting a Finger on Growth Surveillance: Insight into MDM2 Zinc Finger-Ribosomal Protein Interactions

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Mdm2 targets the p53 transcription cofactor JMY for degradation

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Distinct roles of Mdm2 and Mdm4 in red cell production

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Mdm2 in growth signaling and cancer

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Mammalian Numb is a target protein of Mdm2, ubiquitin ligase

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The intestinal epithelium compensates for p53-mediated cell death and guarantees organismal survival

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Induction of PPM1D following DNA-damaging treatments through a conserved p53 response element coincides with a shift in the use of transcription initiation sites

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MDM2 Binding Induces a Conformational Change in p53 That Is Opposed by Heat-shock Protein 90 and Precedes p53 Proteasomal Degradation

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MDM2 Regulates Dihydrofolate Reductase Activity through Monoubiquitination

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Mouse Double Minute 2 Associates with Chromatin in the Presence of p53 and Is Released to Facilitate Activation of Transcription

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Translational research? Ribosome integrity and a new p53 tumor suppressor checkpoint

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Mdm2 exerts pro-apoptotic activities by antagonizing insulin-like growth factor-I-mediated survival

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Loss of one but not twomdm2 null alleles alters the tumour spectrum inp53 null mice

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Ferroptosis as a p53-mediated activity during tumour suppression

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MDM2, MDMX and p53 in oncogenesis and cancer therapy

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The p53 orchestra: Mdm2 and Mdmx set the tone

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Translating p53 into the clinic

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Results of the Phase I trial of RG7112, a small-molecule MDM2 antagonist in leukemia

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The Mdm2–p53 relationship evolves: Mdm2 swings both ways as an oncogene and a tumor suppressor

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MDM4 is a key therapeutic target in cutaneous melanoma

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MDM2 small-molecule antagonist RG7112 activates p53 signaling and regresses human tumors in preclinical cancer models

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Activation of the p53 pathway by small-molecule-induced MDM2 and MDMX dimerization

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Regulation of p53: a collaboration between Mdm2 and MdmX

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Stabilization of Suv39H1 by SirT1 is part of oxidative stress response and ensures genome protection.

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Autophagy promotes mammalian survival by suppressing oxidative stress and p53

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A distinct p53 target gene set predicts for response to the selective p53–HDM2 inhibitor NVP-CGM097

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p53 pathway is involved in cell competition during mouse embryogenesis

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p53-mediated heterochromatin reorganization regulates its cell fate decisions.

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Network Modeling of MDM2 Inhibitor-Oxaliplatin Combination Reveals Biological Synergy in wt-p53 solid tumors

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Aging mice have increased chromosome instability that is exacerbated by elevated Mdm2 expression

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Widespread Overexpression of Epitope-Tagged Mdm4 Does Not Accelerate Tumor Formation <i>In Vi</i><i>vo</i>

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Ubiquitination and Degradation of Mutant p53

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Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53

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Differences in the ubiquitination of p53 by Mdm2 and the HPV protein E6

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Mdm2-independent ubiquitination of P53

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The Mdm2–p53 relationship evolves: Mdm2 swings both ways as an oncogene and a tumor suppressor

Manfredi, J. J. (2010) · Genes &amp; Development · doi:10.1101/gad.1941710 · Cited by 344 · see citing works