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 127
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, LIF in PDAC, Malignant Melanoma, NPM1_new, Prostate Cancer, p53 in cancer, Pancreatic ductal adenocarcinoma (PDA)
Inhibitors Serdemetan; nutlin-3A
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
+ up-regulates activity img/direct-activation.png ubiquitination NUB1 0.281
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination HDAC1 0.475
Publications: 1 Organism: Homo Sapiens
Pathways:Prostate Cancer
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination RUNX3 0.569
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MDM2 0.345
Publications: 8 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation MDM2 0.365
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation MDM2 0.556
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png dephosphorylation MDM2 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation MDM2 0.342
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation MDM2 0.807
Publications: 2 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ 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 img/direct-activation.png phosphorylation MDM2 0.2
Publications: 2 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation MDM2 0.391
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD signaling
+ up-regulates img/direct-activation.png phosphorylation MDM2 0.391
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD signaling
+ up-regulates activity img/direct-activation.png phosphorylation MDM2 0.807
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ up-regulates activity img/direct-activation.png phosphorylation MDM2 0.556
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 0.807
Publications: 1 Organism: Homo Sapiens
Tissue: Kidney
Pathways:FLT3-ITD signaling
+ up-regulates img/direct-activation.png phosphorylation MDM2 0.472
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.345
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png dephosphorylation MDM2 0.357
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
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.756
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
+ up-regulates img/direct-activation.png dephosphorylation MDM2 0.678
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png dephosphorylation MDM2 0.678
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.517
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 0.446
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/direct-activation.png dephosphorylation MDM2 0.388
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png dephosphorylation MDM2 0.388
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png phosphorylation MDM2 0.268
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MDM2 0.714
Publications: 2 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ up-regulates activity img/direct-activation.png phosphorylation MDM2 0.2
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.714
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination KAT2B 0.614
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination MDM2 0.387
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination MDM2 0.331
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 destabilization img/direct_inhibition.png ubiquitination TP53 0.967
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)
+ down-regulates quantity by destabilization img/direct_inhibition.png binding MDM2 0.418
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/indirect-activation.png MDM2 0.718
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding MDM2 0.299
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png binding CDKN1A 0.654
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 PPARG 0.391
Publications: 1 Organism: Homo Sapiens
Pathways:Prostate Cancer
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination SUV39H1 0.403
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png MDM2 0.434
Publications: 1 Organism: Homo Sapiens
Pathways:Pancreatic ductal adenocarcinoma (PDA)
+ up-regulates img/direct-activation.png ubiquitination NOTCH1 0.484
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD signaling
+ down-regulates activity img/direct_inhibition.png binding TP73 0.829
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding MDM2 0.589
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding GNAS 0.397
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination PER2 0.359
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.282
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination ASF1A 0.271
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination PBXIP1 0.288
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png ubiquitination NFATC2 0.31
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png ubiquitination HEXIM1 0.473
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png ubiquitination SIRT6 0.419
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 quantity by destabilization img/direct_inhibition.png ubiquitination IER3 0.349
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination ATXN1 0.343
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 repression img/indirect_inhibition.png transcriptional regulation MDM2 0.372
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination NUMB 0.45
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination, ubiquitination POLQ 0.2
Publications: 2 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination MDM4 0.718
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding MDM2 0.367
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png CDKN1A 0.654
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 img/direct_inhibition.png chemical inhibition MDM2 0.8
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png binding MDM2 0.667
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 activity img/direct_inhibition.png phosphorylation MDM2 0.548
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ down-regulates img/direct_inhibition.png binding EP300 0.684
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, p53 in cancer
+ down-regulates activity img/direct_inhibition.png ubiquitination FOXO4 0.622
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination GRK2 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding MDM2 0.45
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination APEX1 0.42
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination DYRK2 0.56
Publications: 1
+ up-regulates img/direct-activation.png deubiquitination MDM2 0.77
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png ubiquitination MDM2 0.473
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination EID1 0.427
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png phosphorylation MDM2 0.278
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination MDM2 0.375
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation MDM2 0.378
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, miRNA in AML, FLT3-ITD signaling, Pancreatic ductal adenocarcinoma (PDA)
+ down-regulates quantity by destabilization img/direct_inhibition.png binding MDM2 0.322
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination CDKN2AIP 0.372
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png ubiquitination ARRB2 0.437
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png ubiquitination MDM2 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation MDM2 0.385
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination NOTCH4 0.372
Publications: 1 Organism: Homo Sapiens
Tissue: Breast
+ down-regulates img/direct_inhibition.png chemical inhibition MDM2 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination RB1 0.662
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling, Cell cycle: G1/S phase transition, Cell cycle: G2/M phase transition, Luminal Breast Cancer, Malignant Melanoma, p53 in cancer, Pancreatic ductal adenocarcinoma (PDA)
+ down-regulates activity img/direct_inhibition.png relocalization MDM2 0.766
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
+ 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 polyubiquitination KAT5 0.648
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, IDH-TET in AML
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination RPL26 0.508
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png ubiquitination IRF1 0.39
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png polyubiquitination DDX24 0.334
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination OVOL2 0.2
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination RPL6 0.437
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png binding MDM2 0.437
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination IGF1R 0.659
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination HIF1A 0.635
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png binding MDM2 0.718
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation MDM2 0.967
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)