Summary

Name MDM2
Full Name E3 ubiquitin-protein ligase Mdm2
Synonyms Double minute 2 protein, Hdm2, Oncoprotein Mdm2, p53-binding protein Mdm2
Primary ID Q00987
Links - -
Type protein
Relations 95
Pathways Acute Myeloid Leukemia, AML1-ETO in AML, DNMT3A in AML, IDH-TET in AML, miRNA in AML, NPM1 in AML, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, NPM1_new, Prostate Cancer, p53 in cancer, Pancreatic ductal adenocarcinoma (PDA)
Inhibitors nutlin-3A; Serdemetan
Function E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation (PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells (By similarity). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (By similarity). Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 leading to its cytosolic retention rather than mitochondrial localization resulting in decreased supercomplex assembly (interactions between complex I and complex III), decreased complex I activity, ROS production, and apoptosis (PubMed:30879903).

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Modifications Tables

Relations

Regulator Mechanism target score
+ down-regulates img/direct_inhibition.png phosphorylation MDM2 0.351
Publications: 8 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation MDM2 0.804
Publications: 2 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation MDM2 0.542
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation MDM2 0.371
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation MDM2 0.397
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD signaling
+ up-regulates img/direct-activation.png phosphorylation MDM2 0.2
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ up-regulates activity img/direct-activation.png phosphorylation MDM2 0.2
Publications: 3 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, miRNA in AML, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, Triple mutant AML, NPM1_new, Prostate Cancer, Pancreatic ductal adenocarcinoma (PDA)
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation MDM2 0.348
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation MDM2 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MDM2 0.804
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ up-regulates activity img/direct-activation.png phosphorylation MDM2 0.542
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MDM2 0.2
Publications: 2 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png phosphorylation MDM2 0.397
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD signaling
+ up-regulates img/direct-activation.png phosphorylation MDM2 0.804
Publications: 1 Organism: Homo Sapiens
Tissue: Kidney
Pathways:FLT3-ITD signaling
+ up-regulates img/direct-activation.png phosphorylation MDM2 0.478
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.351
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png dephosphorylation MDM2 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png dephosphorylation MDM2 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png dephosphorylation MDM2 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png dephosphorylation MDM2 0.363
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.747
Publications: 5 Organism: Homo Sapiens, In Vitro
Pathways:FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ down-regulates quantity by destabilization img/direct_inhibition.png dephosphorylation MDM2 0.669
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png dephosphorylation MDM2 0.669
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.502
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ up-regulates activity img/direct-activation.png dephosphorylation MDM2 0.431
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png dephosphorylation MDM2 0.374
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png dephosphorylation MDM2 0.374
Publications: 1 Organism: Mus Musculus
+ down-regulates img/direct_inhibition.png phosphorylation MDM2 0.705
Publications: 2 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.705
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination DYRK2 0.551
Publications: 1
+ down-regulates activity img/direct_inhibition.png binding TP73 0.83
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination EID1 0.434
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation MDM2 0.391
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png relocalization MDM2 0.757
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, AML1-ETO in AML, DNMT3A in AML, NPM1 in AML, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Malignant Melanoma, Triple mutant AML, NPM1_new
+ up-regulates quantity by stabilization img/indirect-activation.png MDM2 0.72
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png MDM2 0.439
Publications: 1 Organism: Homo Sapiens
Pathways:Pancreatic ductal adenocarcinoma (PDA)
+ up-regulates activity img/direct-activation.png polyubiquitination DDX24 0.34
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation MDM2 0.291
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation MDM2 0.2
Publications: 1
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination POLQ 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding MDM2 0.456
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png binding MDM2 0.328
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding EP300 0.675
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, p53 in cancer
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation MDM2 0.38
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, miRNA in AML, FLT3-ITD signaling, Pancreatic ductal adenocarcinoma (PDA)
+ up-regulates activity img/direct-activation.png binding MDM2 0.372
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png binding MDM2 0.72
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding MDM2 0.581
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png binding CDKN1A 0.664
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination MDM2 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination MDM2 0.336
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination CDKN2AIP 0.378
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination NUMB 0.456
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination TP53 0.968
Publications: 3 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, AML1-ETO in AML, DNMT3A in AML, IDH-TET in AML, miRNA in AML, NPM1 in AML, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, Triple mutant AML, NPM1_new, Prostate Cancer, p53 in cancer, Pancreatic ductal adenocarcinoma (PDA)
+ up-regulates img/direct-activation.png ubiquitination NOTCH1 0.49
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD signaling
+ down-regulates quantity by destabilization img/direct_inhibition.png binding MDM2 0.424
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition MDM2 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png CDKN1A 0.664
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, p53 in cancer
+ up-regulates quantity by stabilization img/direct-activation.png binding MDM2 0.444
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination MDM2 0.388
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png deubiquitination MDM2 0.762
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination HIF1A 0.628
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination PBXIP1 0.293
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png chemical inhibition MDM2 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png ubiquitination MDM2 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination MDM4 0.72
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation MDM2 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination PER2 0.363
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MDM2 0.66
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/direct-activation.png transcriptional regulation MDM2 0.283
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, AML1-ETO in AML, IDH-TET in AML
+ down-regulates img/direct_inhibition.png ubiquitination NOTCH4 0.378
Publications: 1 Organism: Homo Sapiens
Tissue: Breast
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination PPARG 0.398
Publications: 1 Organism: Homo Sapiens
Pathways:Prostate Cancer
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination MDM2 0.381
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination KAT5 0.639
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, IDH-TET in AML
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation MDM2 0.378
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation MDM2 0.968
Publications: 1 Organism: Mus Musculus
Pathways:Acute Myeloid Leukemia, AML1-ETO in AML, DNMT3A in AML, IDH-TET in AML, miRNA in AML, NPM1 in AML, FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, Triple mutant AML, NPM1_new, Prostate Cancer, p53 in cancer, Pancreatic ductal adenocarcinoma (PDA)