Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

No abstract is available for this paper.

• Publication year

  2017

• Venue

  Nature Structural &Molecular Biology

• Publication date

  2017-05-29

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1038/nsmb.3414PMID 28553961PMCID PMC6205632
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Functional role of TRIM E3 ligase oligomerization and regulation of catalytic activity

  2016cited by this paper
• Structural insights into the catalysis and regulation of E3 ubiquitin ligases

  2016cited by this paper
• Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway

  2016cited by this paper
• Results of the Phase I Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia

  2015cited by this paper
• University of Dundee Structural basis for the RING catalyzed synthesis of K63 linked ubiquitin chains

  2015cited by this paper
• Activation of a primed RING E3-E2-ubiquitin complex by non-covalent ubiquitin.

  2015cited by this paper
• Drugging the p53 pathway: understanding the route to clinical efficacy

  2014cited by this paper
• Autoactivation of the MDM2 E3 Ligase by Intramolecular Interaction

  2014cited by this paper
• Regulation of p53 by Mdm2 E3 ligase function is dispensable in embryogenesis and development, but essential in response to DNA damage.

  2014cited by this paper
• AKT mediates actinomycin D-induced p53 expression

  2014cited by this paper
• Structure of a RING E3 trapped in action reveals ligation mechanism for the ubiquitin-like protein NEDD8.

  2014cited by this paper
• Multiplex Genome Engineering Using CRISPR/Cas Systems

  2013cited by this paper
• MDMX contains an autoinhibitory sequence element

  2013cited by this paper
• Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3

  2013cited by this paper
• Discovery of RG7388, a potent and selective p53-MDM2 inhibitor in clinical development.

  2013cited by this paper
• Small molecules that bind the Mdm2 RING stabilize and activate p53.

  2012cited by this paper
• Structure of an E3:E2~Ub complex reveals an allosteric mechanism shared among RING/U-box ligases.

  2012cited by this paper
• Structure of a RING E3 ligase and ubiquitin-loaded E2 primed for catalysis

  2012cited by this paper
• Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: an exploratory proof-of-mechanism study.

  2012cited by this paper
• Mutational analysis of Mdm2 C-terminal tail suggests an evolutionarily conserved role of its length in Mdm2 activity toward p53 and indicates structural differences between Mdm2 homodimers and Mdm2/MdmX heterodimers

  2012cited by this paper
• Dual Roles of MDM2 in the Regulation of p53: Ubiquitination Dependent and Ubiquitination Independent Mechanisms of MDM2 Repression of p53 Activity.

  2012cited by this paper
• BIRC7–E2 ubiquitin conjugate structure reveals the mechanism of ubiquitin transfer by a RING dimer

  2012cited by this paper
• The p53 inhibitors MDM2/MDMX complex is required for control of p53 activity in vivo

  2011cited by this paper
• Regulation of MDM2 E3 Ligase Activity by Phosphorylation after DNA Damage

  2011cited by this paper
• Mechanism of ubiquitylation by dimeric RING ligase RNF4

  2011cited by this paper
• Heterodimerization of Mdm2 and Mdm4 is critical for regulating p53 activity during embryogenesis but dispensable for p53 and Mdm2 stability

  2011cited by this paper
• Turning the RING Domain Protein MdmX into an Active Ubiquitin-Protein Ligase*

  2010cited by this paper
• Single-vector inducible lentiviral RNAi system for oncology target validation

  2009cited by this paper
• Specific activation of the p53 pathway by low dose actinomycin D: A new route to p53 based cyclotherapy

  2009cited by this paper
• Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans

  2008cited by this paper
• Temporal activation of p53 by a specific MDM2 inhibitor is selectively toxic to tumors and leads to complete tumor growth inhibition

  2008cited by this paper
• E2–BRCA1 RING interactions dictate synthesis of mono- or specific polyubiquitin chain linkages

  2007cited by this paper
• An essential function of the extreme C‐terminus of MDM2 can be provided by MDMX

  2007cited by this paper
• The Mdm2 RING domain C‐terminus is required for supramolecular assembly and ubiquitin ligase activity

  2007cited by this paper
• Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation.

  2007cited by this paper
• Solution structure of the Hdm2 C2H2C4 RING, a domain critical for ubiquitination of p53.

  2006cited by this paper
• HDM2 phosphorylation by MAPKAP kinase 2

  2005cited by this paper
• Coot: model-building tools for molecular graphics.

  2004cited by this paper
• Inhibition of MDM2-mediated p53 Ubiquitination and Degradation by Ribosomal Protein L5*

  2004cited by this paper
• Ribosomal Protein L23 Activates p53 by Inhibiting MDM2 Function in Response to Ribosomal Perturbation but Not to Translation Inhibition

  2004cited by this paper
• The RING domain of Mdm2 mediates histone ubiquitylation and transcriptional repression.

  2004cited by this paper
• In Vivo Activation of the p53 Pathway by Small-Molecule Antagonists of MDM2

  2004cited by this paper
• Critical Role for a Central Part of Mdm2 in the Ubiquitylation of p53

  2003cited by this paper
• MDM2 Promotes Ubiquitination and Degradation of MDMX

  2003cited by this paper
• Electronic Reprint Biological Crystallography Likelihood-enhanced Fast Rotation Functions Biological Crystallography Likelihood-enhanced Fast Rotation Functions

  2003cited by this paper
• The MDM2-p53 interaction.

  2003cited by this paper
• Critical Contribution of the MDM2 Acidic Domain to p53 Ubiquitination

  2003cited by this paper
• HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53

  2003cited by this paper
• DNA Damage-induced MDMX Degradation Is Mediated by MDM2*

  2003cited by this paper
• Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex

  2003cited by this paper
• Mdm4 (Mdmx) Regulates p53-Induced Growth Arrest and Neuronal Cell Death during Early Embryonic Mouse Development

  2002cited by this paper
• MdmX Is a RING Finger Ubiquitin Ligase Capable of Synergistically Enhancing Mdm2 Ubiquitination*

  2002cited by this paper
• mdmx is a negative regulator of p53 activity in vivo.

  2002cited by this paper
• Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53

  2001cited by this paper
• Mdmx stabilizes p53 and Mdm2 via two distinct mechanisms

  2001cited by this paper
• Sensitivity of Mammalian Cells Expressing Mutant Ubiquitin to Protein-damaging Agents*

  2001cited by this paper
• The contribution of the acidic domain of MDM2 to p53 and MDM2 stability

  2001cited by this paper
• The MDM2 RING-finger domain is required to promote p53 nuclear export

  2000cited by this paper
• Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases.

  2000cited by this paper
• Hdmx stabilizes Mdm2 and p53.

  2000cited by this paper
• MdmX Protects p53 from Mdm2-Mediated Degradation

  2000cited by this paper
• Analysis of the degradation function of Mdm2.

  1999cited by this paper
• Stabilization of the MDM2 Oncoprotein by Interaction with the Structurally Related MDMX Protein*

  1999cited by this paper
• Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53

  1997cited by this paper
• Wild-type and mutant p53 differentially regulate transcription of the insulin-like growth factor I receptor gene.

  1996cited by this paper
• Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53

  1995cited by this paper
• Regulation of Transcription Functions of the p53 Tumor Suppressor by the mdm-2 Oncogene

  1995cited by this paper
• Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53

  1995cited by this paper
• The CCP4 suite: programs for protein crystallography.

  1994cited by this paper
• Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53

  1993cited by this paper
• The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation.

  1992cited by this paper
• Electronic Reprint Biological Crystallography Phenix: Building New Software for Automated Crystallographic Structure Determination Biological Crystallography Phenix: Building New Software for Automated Crystallographic Structure Determination

  year unknowncited by this paper

• Tuning ubiquitin transfer by RING E3 ubiquitin ligases through the linchpin residue

  2025cites this paper
• Exploring the heterodimer MDM2/MDM4 interaction region uncovers high-affinity peptides for therapeutic p53-reactivation

  2025cites this paper
• Structure and function of MDM2 and MDM4 in health and disease

  2025influential citation
• Targeting MDM2 homodimer and heterodimer disruption with DRx-098D in TP53 wild-type and mutant cancer cells

  2025cites this paper
• MDM2 functions as a timer reporting the length of mitosis

  2025cites this paper
• UBA6 specificity for ubiquitin E2 conjugating enzymes reveals a priority mechanism of BIRC6.

  2025cites this paper
• Characterizing Elephant MDM2's Role in p53 Regulation

  2025cites this paper
• MDM2 acts as a timer reporting the length of mitosis

  2024cites this paper
• Chemical Tools for Probing the Ub/Ubl Conjugation Cascades

  2024cites this paper
• Mapping Full Conformational Transition Dynamics of Intrinsically Disordered Proteins Using a Single-Molecule Nanocircuit.

  2024cites this paper
• Cellular, Structural Basis, and Recent Progress for Targeting Murine Double Minute X (MDMX) in Tumors.

  2024cites this paper
• Plausible, robust biological oscillations through allelic buffering.

  2024cites this paper
• Rational design, synthesis, and biophysical characterization of a peptidic MDM2-MDM4 interaction inhibitor.

  2024cites this paper
• MDM2 acts as a timer reporting the length of mitosis

  2023cites this paper
• Multisite phosphorylation dictates selective E2-E3 pairing as revealed by Ubc8/UBE2H-GID/CTLH assemblies.

  2023cites this paper
• Cullin7 induces docetaxel resistance by regulating the protein level of the antiapoptotic protein Survivin in lung adenocarcinoma cells

  2023cites this paper
• Identification of a Novel Heterogeneous Nuclear Ribonucleoprotein A2B1 (hnRNPA2B1) Ligand that Disrupts HnRNPA2B1/Nucleic Acid Interactions to Inhibit the MDMX-p53 Axis in Gastric Cancer.

  2023cites this paper
• MDM2 promotes cancer cell survival through regulating the expression of HIF-1α and pVHL in retinoblastoma

  2023cites this paper
• Substrate trapping approach identifies TRIM25 ubiquitination targets involved in diverse cellular and antiviral processes

  2022cites this paper
• Elucidation of TRIM25 ubiquitination targets involved in diverse cellular and antiviral processes

  2022cites this paper
• Bivalent binding of p14ARF to MDM2 RING and acidic domains inhibits E3 ligase function

  2022cites this paper
• Structural studies of antitumor compounds that target the RING domain of MDM2

  2022cites this paper
• Repressed miR-34a Expression Dictates the Cell Fate to Corneal Endothelium Failure

  2022cites this paper
• Targeted Degradation of 53BP1 Using Ubiquitin Variant Induced Proximity

  2022cites this paper
• Ubiquitin and a charged loop regulate the ubiquitin E3 ligase activity of Ark2C

  2022cites this paper
• Alterations of the MDM2 C-terminus differentially impact its function in vivo.

  2022cites this paper
• BCAS3 exhibits oncogenic properties by promoting CRL4A‐mediated ubiquitination of p53 in breast cancer

  2021cites this paper
• Identification of a Catalytic Active but Non-Aggregating MDM2 RING Domain Variant

  2021influential citation
• The structure and ubiquitin binding properties of TRAF RING heterodimers.

  2021cites this paper
• Cullin7 in tumor development: a novel potential anti-cancer target.

  2021cites this paper
• Nutrient copper signaling promotes protein turnover by allosteric activation of ubiquitin E2D conjugases

  2021cites this paper
• GID E3 ligase supramolecular chelate assembly configures multipronged ubiquitin targeting of an oligomeric metabolic enzyme

  2021cites this paper
• Studying Homo-oligomerization and Hetero-oligomerization of MDMX and MDM2 Proteins in Single Living Cells by Using In Situ Fluorescence Correlation Spectroscopy.

  2021cites this paper
• An E3 ligase guide to the galaxy of small-molecule-induced protein degradation.

  2021cites this paper
• Inhibition of p22phox Suppresses Epithelial Ovarian Cancer Cell Proliferation and Tumorigenesis

  2021cites this paper
• MDMX is essential for the regulation of p53 protein levels in the absence of a functional MDM2 C-terminal tail

  2021cites this paper
• Proteasomal Degradation of Zn-Dependent Hdacs: The E3-Ligases Implicated and the Designed Protacs That Enable Degradation

  2021cites this paper
• Understanding the interaction of 14‐3‐3 proteins with hDMX and hDM2: a structural and biophysical study

  2021cites this paper
• Inhibition of Mdm2 ubiquitin-ligase activity by PRDX1 leads to the activation of p53 tumor suppressor

  2021cites this paper
• Differential requirements for MDM2 E3 activity during embryogenesis and in adult mice

  2020cites this paper
• How to Inactivate Human Ubiquitin E3 Ligases by Mutation

  2020cites this paper
• Structural insights into ADP-ribosylation of ubiquitin by Deltex family E3 ubiquitin ligases

  2020cites this paper
• CMAR_A_260943 7715..7724

  2020cites this paper
• MDM2-C Functions as an E3 Ubiquitin Ligase

  2020cites this paper
• Tp53 Suppression Promotes Cardiomyocyte Proliferation during Zebrafish Heart Regeneration

  2020cites this paper
• Targeted modulation of E3 ligases using engineered ubiquitin variants

  2020cites this paper
• Structural basis for DNA damage-induced phosphoregulation of MDM2 RING domain

  2020cites this paper
• Mdm2: Open questions

  2020cites this paper
• Mdm2 and MdmX RING Domains Play Distinct Roles in the Regulation of p53 Responses: A Comparative Study of Mdm2 and MdmX RING Domains in U2OS Cells

  2020cites this paper
• TOP2A Promotes Lung Adenocarcinoma Cells' Malignant Progression and Predicts Poor Prognosis in Lung Adenocarcinoma

  2020cites this paper
• Structural basis of generic versus specific E2–RING E3 interactions in protein ubiquitination

  2019cites this paper
• A Single Conserved Amino Acid Residue as a Critical Context-Specific Determinant of the Differential Ability of Mdm2 and MdmX RING Domains to Dimerize

  2019cites this paper
• Competitive ubiquitination activates the tumor suppressor p53

  2019cites this paper
• Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma

  2019cites this paper
• A Designed Peptide Targets Two Types of Modifications of p53 with Anti-cancer Activity.

  2018cites this paper
• LACTB, a novel epigenetic silenced tumor suppressor, inhibits colorectal cancer progression by attenuating MDM2-mediated p53 ubiquitination and degradation

  2018cites this paper
• MANF attenuates neuronal apoptosis and promotes behavioral recovery via Akt/MDM‐2/p53 pathway after traumatic spinal cord injury in rats

  2018cites this paper
• A GYS2/p53 negative feedback loop restricts tumor growth in HBV-related hepatocellular carcinoma

  2018cites this paper
• Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response

  2018influential citation
• Zinc deficiency causes neural tube defects through attenuation of p53 ubiquitylation

  2018cites this paper
• Structural insights into non-covalent ubiquitin activation of the cIAP1-UbcH5B∼ubiquitin complex

  2018influential citation
• Strategies to Trap Enzyme-Substrate Complexes that Mimic Michaelis Intermediates During E3-Mediated Ubiquitin-Like Protein Ligation.

  2018cites this paper
• Structural and functional characterization of hMEX‐3C Ring finger domain as an E3 ubiquitin ligase

  2018influential citation
• Maternal undernutrition during early pregnancy inhibits postnatal growth of the tibia in the female offspring of rats by alteration of chondrogenesis.

  2017cites this paper
• Scholarly Commons @ Baptist Health South Florida Scholarly Commons @ Baptist Health South Florida

  year unknowncites this paper