GenAge entry for MDM2 (Homo sapiens)

Gene name (HAGRID: 210)

HGNC symbol: MDM2
Aliases: HDM2; MGC5370
Common name: MDM2 proto-oncogene, E3 ubiquitin protein ligase

Potential relevance to the human ageing process

Main reason for selection: Entry selected based on evidence linking the gene product to the regulation or control of genes previously linked to ageing
Description: MDM2 is an oncogene that inhibits TP53 [890]. The MDM2 gene encodes multiple transcripts, many of which are tissue-specific. Disruption of MDM2 in mice resulted in increased TP53-dependent apoptosis and defects in multiple haematopoietic lineages [889]. Mutations in the human MDM2 gene have been associated with cancer [1738]. A role for MDM2 in human ageing is unknown.

Cytogenetic information

Cytogenetic band: 12q14.3-q1
Location: 68,808,172 bp to 68,845,544 bp
Orientation: Plus strand

Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology

Process:

GO:0000122; negative regulation of transcription from RNA polymerase II promoter
GO:0001568; blood vessel development
GO:0001974; blood vessel remodeling
GO:0002027; regulation of heart rate
GO:0003181; atrioventricular valve morphogenesis
GO:0003203; endocardial cushion morphogenesis
GO:0003281; ventricular septum development
GO:0003283; atrial septum development
GO:0006461; protein complex assembly
GO:0006977; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0007089; traversing start control point of mitotic cell cycle

And 48 more GO terms

Cellular component:

GO:0005634; nucleus
GO:0005654; nucleoplasm
GO:0005730; nucleolus
GO:0005737; cytoplasm
GO:0005829; cytosol
GO:0005886; plasma membrane
GO:0016604; nuclear body
GO:0030666; endocytic vesicle membrane
GO:0043234; protein complex
GO:0045202; synapse

Function:

GO:0002039; p53 binding
GO:0004842; ubiquitin-protein transferase activity
GO:0005515; protein binding
GO:0008270; zinc ion binding
GO:0016874; ligase activity
GO:0019789; SUMO transferase activity
GO:0019899; enzyme binding
GO:0031625; ubiquitin protein ligase binding
GO:0042802; identical protein binding
GO:0042975; peroxisome proliferator activated receptor binding
GO:0061630; ubiquitin protein ligase activity

And 2 more GO terms

Show all GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge: TP53, TERT, ATM, ERCC8, IGF1R, E2F1, AKT1, NBN, JUND, CREBBP, HIF1A, S100B, VCP, HSP90AA1, NR3C1, EGR1, ABL1, TOP1, UBE2I, ERCC6, EP300, PML, GSK3B, EEF2, AR, PCNA, XRCC6, RB1, FOXO3, FOXO1, UCHL1, APP, RELA, HDAC1, PTK2, JUN, MED1, TAF1, SDHC, FOXO4, EEF1A1, TBP, APEX1, BUB1B, HSPA8, MDM2, SUMO1, ESR1, CLU, CDKN2A, PPP1CA, TP63, SIRT6, PPM1D, CHEK2, PPARG, TP73, CDKN1A
STRING interaction network

Retrieve sequences for MDM2

ORF: ORF
CDS: CDS

Homologs in model organisms

Danio rerio: mdm2
Mus musculus: Mdm2
Rattus norvegicus: Mdm2

In other databases

LongevityMap

This gene is present as MDM2

CellAge

This gene is present as MDM2

CellAge gene expression

This gene is present as MDM2

Selected references

[3313] Pant et al. (2013) "The p53-Mdm2 feedback loop protects against DNA damage by inhibiting p53 activity but is dispensable for p53 stability, development, and longevity." Genes Dev. 27(17):1857-1867 (PubMed)
[1603] Mendrysa et al. (2006) "Tumor suppression and normal aging in mice with constitutively high p53 activity." Genes Dev. 20(1):16-21 (PubMed)
[1822] Sablina et al. (2005) "The antioxidant function of the p53 tumor suppressor." Nat. Med. 11(12):1306-1313 (PubMed)
[1738] Bond et al. (2004) "A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans." Cell 119(5):591-602 (PubMed)
[1146] Maier et al. (2004) "Modulation of mammalian life span by the short isoform of p53." Genes Dev. 18(3):306-319 (PubMed)
[889] Mendrysa et al. (2003) "mdm2 Is critical for inhibition of p53 during lymphopoiesis and the response to ionizing irradiation." Mol. Cell. Biol. 23(2):462-472 (PubMed)
[888] Alt et al. (2003) "Mdm2 haplo-insufficiency profoundly inhibits Myc-induced lymphomagenesis." EMBO J. 22(6):1442-1450 (PubMed)
[1673] Das et al. (2001) "Ionizing radiation down-regulates p53 protein in primary Egr-1-/- mouse embryonic fibroblast cells causing enhanced resistance to apoptosis." J. Biol. Chem. 276(5):3279-3286 (PubMed)
[1038] Maya et al. (2001) "ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage." Genes Dev. 15(9):1067-1077 (PubMed)
[1405] Pomerantz et al. (1998) "The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53." Cell 92(6):713-723 (PubMed)
Show all references (1 more)