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MDM2 proto-oncogene

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Target not currently curated in GtoImmuPdb

Target id: 3136

Nomenclature: MDM2 proto-oncogene

Family: E3 ubiquitin ligase components

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 497 12q15 MDM2 MDM2 proto-oncogene
Mouse - 489 10 D2; 10 66.32 cM Mdm2 transformed mouse 3T3 cell double minute 2
Rat - 458 7q22 Mdm2 MDM2 proto-oncogene
Gene and Protein Information Comments
Alternative splicing of the human gene results in a multitude of transcript variants and protein isoforms. Many of these isoforms have been detected only in tumour cells.
Previous and Unofficial Names Click here for help
E3 ubiquitin-protein ligase Mdm2 | p53-binding protein Mdm2 | RING-type E3 ubiquitin transferase Mdm2
Database Links Click here for help
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 2.3.2.27

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
AMG-232 Small molecule or natural product Hs Inhibition 10.4 pKd 4
pKd 10.4 (Kd 4.5x10-11 M) [4]
Description: Binding affinity determined in a SPR assay, measuring inhibition of interaction between human p53 and recombinant MDM2.
RG7112 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Binding - - 5
[5]
Biologically Significant Variant Comments
Splice variants which don't contain p53 binding domain sequences are found in late-stage and high-grade ovarian and bladder carcinomas.
General Comments
MDM2 is a nuclear E3 ubiquitin-protein ligase. It can promote tumour formation by targeting the p53 tumour suppressor protein for proteasomal degradation [1-3]. MDM2 expression is regulated by p53 transcriptional activity.

References

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1. Momand J, Zambetti GP, Olson DC, George D, Levine AJ. (1992) The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell, 69 (7): 1237-45. [PMID:1535557]

2. Ries S, Biederer C, Woods D, Shifman O, Shirasawa S, Sasazuki T, McMahon M, Oren M, McCormick F. (2000) Opposing effects of Ras on p53: transcriptional activation of mdm2 and induction of p19ARF. Cell, 103 (2): 321-30. [PMID:11057904]

3. Sasaki M, Kawahara K, Nishio M, Mimori K, Kogo R, Hamada K, Itoh B, Wang J, Komatsu Y, Yang YR et al.. (2011) Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11. Nat. Med., 17 (8): 944-51. [PMID:21804542]

4. Sun D, Li Z, Rew Y, Gribble M, Bartberger MD, Beck HP, Canon J, Chen A, Chen X, Chow D et al.. (2014) Discovery of AMG 232, a potent, selective, and orally bioavailable MDM2-p53 inhibitor in clinical development. J. Med. Chem., 57 (4): 1454-72. [PMID:24456472]

5. Vu B, Wovkulich P, Pizzolato G, Lovey A, Ding Q, Jiang N, Liu JJ, Zhao C, Glenn K, Wen Y et al.. (2013) Discovery of RG7112: A Small-Molecule MDM2 Inhibitor in Clinical Development. ACS Med Chem Lett, 4 (5): 466-9. [PMID:24900694]

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