Yksinkertainen RNF tyyppinen E3 ubikitiiniligaasi MDM2

MDM2 on proto-onkogeeni. Yksinkertainen RING- rakenteinen E3 ubkitiniiligaasi.
Muut nimet ovat HDMX,hdm2, ACTFS
 Sinkkisormiproteiinien joukossa ryhmää RNF,  Zf-RANBP
Zn finger rakenne CxCxCxHxxxCxCxCxCx.
 https://www.ncbi.nlm.nih.gov/gene/4193

Also known as

HDMX; hdm2; ACTFS

Summary: This gene encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. This gene is itself transcriptionally-regulated by p53. Overexpression or amplification of this locus is detected in a variety of different cancers. There is a pseudogene for this gene on chromosome 2. Alternative splicing results in a multitude of transcript variants, many of which may be expressed only in tumor cells. [provided by RefSeq, Jun 2013]

Expression Ubiquitous expression in colon (RPKM 13.6), bone marrow (RPKM 9.8) and 25 other tissues See more Orthologs mouse all

Preferred Names

E3 ubiquitin-protein ligase Mdm2

Conserved Domains (3) summary

pfam00641
Location:252 → 281

zf-RanBP; Zn-finger in Ran binding protein and others

pfam02201
Location:45 → 92

SWIB; SWIB/MDM2 domainThis family includes the SWIB domain and the MDM2 domain. The p53-associated protein (MDM2) is an inhibitor of the p53 tumour suppressor gene binding the transactivation domain and down regulating the ability of p53 to activate transcription. This family contains the p53 binding domain of MDM2.

pfam13920
Location:389 → 436

zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)

 

Names

MDM2 oncogene, E3 ubiquitin protein ligase

MDM2 proto-oncogene, E3 ubiquitin protein ligase

Mdm2, p53 E3 ubiquitin protein ligase homolog

Mdm2, transformed 3T3 cell double minute 2, p53 binding protein

double minute 2, human homolog of; p53-binding protein

oncoprotein Mdm2

Related articles in PubMed

1. Renal Epithelioid Angiomyolipoma Undergoing Aggressive Clinical Outcome: The MDM2 Expression in Tumor Cells of Two Cases. Inoue C, et al. Tohoku J Exp Med, 2019 Feb. PMID 30799331
2. Association between MDM2 SNP309 and endometrial cancer risk: A PRISMA-compliant meta-analysis. Zou X, et al. Medicine (Baltimore), 2018 Dec. PMID 30544386, Free PMC Article
3. The Study of MDM2 rs937283 Variant and Cancer Susceptibility in a Central Chinese Population. Chen B, et al. Technol Cancer Res Treat, 2018 Jan 1. PMID 30244662, Free PMC Article
4. Contribution of Murine Double Minute 2 Genotypes to Colorectal Cancer Risk in Taiwan. Yueh TC, et al. Cancer Genomics Proteomics, 2018 Sep-Oct. PMID 30194081, Free PMC Article
5. The MDM2 rs937283 A > G variant significantly increases the risk of lung and gastric cancer in Chinese population. Chen B, et al. Int J Clin Oncol, 2018 Oct. PMID 29777315

See all (1813) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

1. Expression of MDM2 and Bcl2 was significantly up-regulated, while Bax was down-regulated in renal cell carcinoma as compared with normal kidney tissue.
2. The study shows complex interrelation between apoptosis and cell cycle regulating proteins (MDM2, BCL2 and Bax) in benign prostatic hyperplasia and prostate cancer.
3. role of TNFAIP8 in NSCLC proliferation and cisplatin chemoresistance that is mediated through the MDM2/p53 pathway
4. MDM2 is critically involved in regulating WRN function via ubiquitin-dependent degradation and reveal an unexpected role of MDM2 in promoting cellular senescence through a p53-independent manner.
5. H3K9ac was a specific target for Ras-ERK1/2 signaling pathway. H3K9 acetylation can be modulated by HDAC2 and MDM2-depedent degradation of PCAF. The revealed regulation provides a better understanding of Ras-ERK1/2 signaling in tumorigenesis.
6. this is the first study demonstrating that MDM2 could play an important role in the molecular mechanisms of recurrence/metastasis of Epithelioid angiomyolipoma.
7. High-level MDM2 amplification determined by FISH strongly favors dedifferentiated liposarcoma over malignant peripheral nerve sheath tumor.
8. Chromatin modification by Mdm2 and PRC1 ensures smooth DNA replication through the avoidance of R-loop formation.
9. Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response.
10. HDMX and HDM2 interact via their respective C-terminal RING domains but here we show that the presence of p53 induces an N-terminal interface under normal cellular conditions.

Submit: New GeneRIF Correction See all GeneRIFs (1201)

• In one article, there is told about MDM4.

•  Here I look also   data about MDM4 (1q32.1)
• https://www.ncbi.nlm.nih.gov/gene/4194

Also known as

HDMX; MDMX; MRP1

Summary

This gene encodes a nuclear protein that contains a p53 binding domain at the N-terminus and a RING finger domain at the C-terminus, and shows structural similarity to p53-binding protein MDM2. Both proteins bind the p53 tumor suppressor protein and inhibit its activity, and have been shown to be overexpressed in a variety of human cancers. However, unlike MDM2 which degrades p53, this protein inhibits p53 by binding its transcriptional activation domain. This protein also interacts with MDM2 protein via the RING finger domain, and inhibits the latter's degradation. So this protein can reverse MDM2-targeted degradation of p53, while maintaining suppression of p53 transactivation and apoptotic functions. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Feb 2011]

ExpressionUbiquitous expression in bone marrow (RPKM 9.7), skin (RPKM 6.5) and 24 other tissues See more Orthologs mouse all

Conserved Domains (2) summary

pfam00641
Location:250 → 279

zf-RanBP; Zn-finger in Ran binding protein and others

pfam13920
Location:385 → 432

zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)

Preferred Names

protein Mdm4

Names

MDM4 protein variant G

MDM4 protein variant Y

MDM4, p53 regulator

MDM4-related protein 1

Mdm4 p53 binding protein homolog

double minute 4, human homolog of; p53-binding protein

mdm2-like p53-binding protein

protein Mdmx

  Some references:

GeneRIFs: Gene References Into Functions

1. MDM4 gain, APC loss, and FBXW7 loss are the independent prognostic factors for extrohepatic metastasis-free survival after the operation for HCC[hepatocellular carcinoma ] and can be used to predict the risk of extrohepatic metastasis after the operation for HCC.
2. Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response.
3. A combination of MDM4/MDM2 knockdown and conventional cytotoxic drugs could be a promising treatment strategy for wtTP53/highMDM4 gastrointestinal cancers.
4. Mdm4 role in the cisplatin resistance in breast cancer.Mdm4 is the target gene of miR-1307 in the breast cancer.
5. MDM4 polymorphisms may, individually or in combination, confer an independent risk of squamous cell carcinoma of the oropharynx recurrence, particularly in HPV-positive SCCOP patients.
6. It has been shown that MDM2 and MDMX are targetable vulnerabilities within TP53-wild-type T-cell lymphomas.
7. Considering the lack of association between MDM4 rs4245739 polymorphism and breast cancer, rs4245739 polymorphism of this gene seems to have no significant role in the pathophysiology of the disease.
8. In multivariate analysis, MDM2/MDM4 and EGFR alterations correlated with time-to-treatment failure (TTF)..Some patients with MDM2 family amplification or EGFR aberrations had poor clinical outcome and significantly increased rate of tumor growth after single-agent checkpoint (PD-1/PD-L1) inhibitors
9. We conclude that Mdm4-S overexpression is a consequence of splicing defects in tumor cells rather than a cause of tumor evolution.
10. These results indicate that the rs4245739 polymorphism may contribute to a decreased cancer susceptibility and support the hypothesis that genetic variants in the MDM4 genes act as important modifiers of cancer risk.