Target Information

Target General Information

Target ID

T10937 (Former ID: TTDR01399)

Target Name

Mdm2 messenger RNA (MDM2 mRNA)

Synonyms

RING-type E3 ubiquitin transferase Mdm2 (mRNA); P53-binding protein Mdm2 (mRNA); Oncoprotein Mdm2 (mRNA); MDM2 protein (mRNA); Hdm2 (mRNA); E3 ubiquitin-protein ligase Mdm2 (mRNA); Double minute 2 protein (mRNA)

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Gene Name

MDM2

Target Type

Literature-reported target

[1]

Disease

[+] 1 Target-related Diseases

Solid tumour/cancer [ICD-11: 2A00-2F9Z]

Function

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. Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells. Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis. E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome.

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BioChemical Class

mRNA target

UniProt ID

MDM2_HUMAN

EC Number

EC 2.3.2.27

Sequence

MCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQY
IMTKRLYDEKQQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVNQQESSDSGT
SVSENRCHLEGGSDQKDLVQELQEEKPSSSHLVSRPSTSSRRRAISETEENSDELSGERQ
RKRHKSDSISLSFDESLALCVIREICCERSSSSESTGTPSNPDLDAGVSEHSGDWLDQDS
VSDQFSVEFEVESLDSEDYSLSEEGQELSDEDDEVYQVTVYQAGESDTDSFEEDPEISLA
DYWKCTSCNEMNPPLPSHCNRCWALRENWLPEDKGKDKGEISEKAKLENSTQAEEGFDVP
DCKKTIVNDSRESCVEENDDKITQASQSQESEDYSQPSTSSSIIYSSQEDVKEFEREETQ
DKEESVESSLPLNAIEPCVICQGRPKNGCIVHGKTGHLMACFTCAKKLKKRNKPCPVCRQ
PIQMIVLTYFP

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Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Property Profile of Target

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(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Target Affiliated Biological Pathways		Top
KEGG Pathway	[+] 18 KEGG Pathways	+
1	FoxO signaling pathway
2	Cell cycle
3	p53 signaling pathway
4	Ubiquitin mediated proteolysis
5	Endocytosis
6	PI3K-Akt signaling pathway
7	Thyroid hormone signaling pathway
8	Epstein-Barr virus infection
9	Pathways in cancer
10	Transcriptional misregulation in cancer
11	Viral carcinogenesis
12	Proteoglycans in cancer
13	MicroRNAs in cancer
14	Glioma
15	Prostate cancer
16	Melanoma
17	Bladder cancer
18	Chronic myeloid leukemia
Panther Pathway	[+] 5 Panther Pathways	+
1	Insulin/IGF pathway-protein kinase B signaling cascade
2	p53 pathway
3	Ubiquitin proteasome pathway
4	P53 pathway feedback loops 1
5	p53 pathway feedback loops 2
PID Pathway	[+] 13 PID Pathways	+
1	ErbB4 signaling events
2	p73 transcription factor network
3	ATR signaling pathway
4	ATM pathway
5	Glucocorticoid receptor regulatory network
6	Sumoylation by RanBP2 regulates transcriptional repression
7	Direct p53 effectors
8	Regulation of Androgen receptor activity
9	Validated transcriptional targets of deltaNp63 isoforms
10	Aurora A signaling
11	Validated transcriptional targets of TAp63 isoforms
12	p53 pathway
13	Regulation of retinoblastoma protein
Reactome	[+] 6 Reactome Pathways	+
1	AKT phosphorylates targets in the cytosol
2	Oxidative Stress Induced Senescence
3	Oncogene Induced Senescence
4	Trafficking of AMPA receptors
5	Constitutive Signaling by AKT1 E17K in Cancer
6	Stabilization of p53
WikiPathways	[+] 22 WikiPathways	+
1	DNA Damage Response (only ATM dependent)
2	DNA Damage Response
3	Senescence and Autophagy in Cancer
4	Tryptophan metabolism
5	G1 to S cell cycle control
6	Copper homeostasis
7	Bladder Cancer
8	Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic Cell
9	PIP3 activates AKT signaling
10	Apoptosis
11	ATM Signaling Pathway
12	Retinoblastoma (RB) in Cancer
13	Integrated Pancreatic Cancer Pathway
14	Prostate Cancer
15	Signaling Pathways in Glioblastoma
16	Integrated Breast Cancer Pathway
17	Integrated Cancer pathway
18	Cell Cycle
19	Cell Cycle Checkpoints
20	TP53 Network
21	miRNA Regulation of DNA Damage Response
22	Androgen receptor signaling pathway

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

US patent application no. 6,238,921, Antisense oligonucleotide modulation of human mdm2 expression.

REF 2

Discovery of a nanomolar inhibitor of the human murine double minute 2 (MDM2)-p53 interaction through an integrated, virtual database screening str... J Med Chem. 2006 Jun 29;49(13):3759-62.

REF 3

Small-molecule inhibitors of the MDM2-p53 protein-protein interaction based on an isoindolinone scaffold. J Med Chem. 2006 Oct 19;49(21):6209-21.

REF 4

Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature. 2007 Dec 13;450(7172):1001-9.

REF 5

Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction. J Med Chem. 2006 Jun 15;49(12):3432-5.

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