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 121
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 0.277
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination HDAC1 0.469
Publications: 1 Organism: Homo Sapiens
Pathways:Prostate Cancer
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination RUNX3 0.577
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MDM2 0.346
Publications: 8 Organism: Homo Sapiens
+ 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 0.811
Publications: 2 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation MDM2 0.558
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation MDM2 0.39
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD signaling
+ up-regulates quantity by stabilization img/direct-activation.png phosphorylation MDM2 0.343
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 0.365
Publications: 1 Organism: Homo Sapiens
Pathways: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 0.811
Publications: 1 Organism: Homo Sapiens
Pathways:FLT3-ITD signaling
+ up-regulates img/direct-activation.png phosphorylation MDM2 0.39
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD signaling
+ up-regulates activity img/direct-activation.png phosphorylation MDM2 0.558
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 0.811
Publications: 1 Organism: Homo Sapiens
Tissue: Kidney
Pathways:FLT3-ITD signaling
+ up-regulates img/direct-activation.png phosphorylation MDM2 0.467
Publications: 2 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.346
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 0.357
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
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.755
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 0.68
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png dephosphorylation MDM2 0.68
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.52
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 0.452
Publications: 1 Organism: Mus Musculus
+ up-regulates activity img/direct-activation.png dephosphorylation MDM2 0.397
Publications: 1 Organism: Mus Musculus
+ up-regulates img/direct-activation.png dephosphorylation MDM2 0.397
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png phosphorylation MDM2 0.715
Publications: 2 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.715
Publications: 1 Organism: Homo Sapiens
Pathways:Cell cycle: G2/M phase transition
+ up-regulates quantity by stabilization img/direct-activation.png binding MDM2 0.435
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination NUMB 0.445
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation MDM2 0.373
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 0.324
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination, ubiquitination POLQ 0.2
Publications: 2 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding MDM2 0.365
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png ubiquitination ARRB2 0.435
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/indirect_inhibition.png MDM2 0.43
Publications: 1 Organism: Homo Sapiens
Pathways:Pancreatic ductal adenocarcinoma (PDA)
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination PBXIP1 0.29
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding MDM2 0.445
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png CDKN1A 0.646
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 expression img/indirect-activation.png transcriptional regulation MDM2 0.286
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination RPL26 0.5
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)
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination PPARG 0.39
Publications: 1 Organism: Homo Sapiens
Pathways:Prostate 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 0.672
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 KAT2B 0.62
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 ubiquitination IER3 0.35
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png relocalization MDM2 0.764
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 polyubiquitination KAT5 0.652
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, IDH-TET in AML
+ down-regulates img/direct_inhibition.png chemical inhibition MDM2 0.8
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png binding EP300 0.686
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, p53 in cancer
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination ATXN1 0.335
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination ASF1A 0.267
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)
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination APEX1 0.417
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity img/direct_inhibition.png ubiquitination NFATC2 0.306
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination RB1 0.666
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 quantity by destabilization img/direct_inhibition.png binding CDKN1A 0.646
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 activity img/direct_inhibition.png binding TP73 0.837
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png binding MDM2 0.415
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png ubiquitination MDM2 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png binding MDM2 0.597
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/direct-activation.png transcriptional regulation MDM2 0.279
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 polyubiquitination EID1 0.425
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding MDM2 0.3
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png binding MDM2 0.732
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png binding GNAS 0.395
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png phosphorylation MDM2 0.279
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation MDM2 0.2
Publications: 1
+ down-regulates quantity img/direct_inhibition.png ubiquitination SIRT6 0.416
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png deubiquitination MDM2 0.77
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination NOTCH4 0.371
Publications: 1 Organism: Homo Sapiens
Tissue: Breast
+ up-regulates activity img/direct-activation.png polyubiquitination DDX24 0.335
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by repression img/indirect_inhibition.png transcriptional regulation MDM2 0.371
Publications: 1 Organism: Homo Sapiens
+ up-regulates activity img/direct-activation.png ubiquitination HEXIM1 0.467
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination MDM2 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/direct-activation.png ubiquitination MDM2 0.468
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination MDM2 0.38
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination MDM4 0.732
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination PER2 0.357
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by stabilization img/indirect-activation.png MDM2 0.732
Publications: 1 Organism: Homo Sapiens
+ down-regulates activity img/direct_inhibition.png ubiquitination FOXO4 0.629
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination SUV39H1 0.401
Publications: 1 Organism: Homo Sapiens
+ down-regulates img/direct_inhibition.png ubiquitination CDKN2AIP 0.371
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination RPL6 0.434
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination HIF1A 0.641
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination GRK2 0.2
Publications: 1 Organism: Homo Sapiens
+ up-regulates quantity by expression img/indirect-activation.png transcriptional regulation MDM2 0.384
Publications: 1 Organism: Homo Sapiens
+ up-regulates img/direct-activation.png ubiquitination NOTCH1 0.478
Publications: 1 Organism: Homo Sapiens
Pathways:Acute Myeloid Leukemia, FLT3-ITD signaling
+ down-regulates quantity img/direct_inhibition.png ubiquitination IRF1 0.389
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination IGF1R 0.661
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination MDM2 0.331
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination MDM2 0.375
Publications: 1 Organism: Homo Sapiens
+ down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination DYRK2 0.568
Publications: 1