What does the MDM2 gene do?

The murine double minute 2 (mdm2) gene encodes a negative regulator of the p53 tumor suppressor. Amplification of mdm2 or increased expression by unknown mechanisms occurs in many tumors.

Is MDM2 a cancer?

MDM2 is an oncogene with both p53-dependent and p53-independent oncogenic activities, and often has increased expression levels in a variety of human cancers. MDM2 is highly regulated; the levels and function of MDM2 are regulated at the transcriptional, translational and post-translational levels.

Does MDM2 inhibit p53?

The MDM2 protein is a negative regulator of p53. After binding to p53, it inhibits its transcriptional activity, favours its nuclear export and stimulates its degradation. The overexpression of MDM2 in various tumours inhibits p53, therefore favouring uncontrolled cell proliferation.

What is MDM2 in cell cycle?

Mdm2, another p53 target gene, encodes a ubiquitin ligase that negatively regulates p53 levels by ubiquitination. Ablation of Mdm2 by siRNA led to an increase in p53 protein and repression of Cdc25C gene expression. However, Cdc25C protein levels were actually increased following Mdm2 depletion.

How does MDM2 regulate p53?

MDM2 negatively regulates p53 by targeting the ubiquitin ligase activity of MDM2. A complementary approach to prevent p53 degradation by MDM2 is to develop agents designed to inhibit the E3 ligase activity of MDM2 directly so as to mimic the effects of ARF or the ribosomal protein L11.

Is p53 a gene or a protein?

A gene that makes a protein that is found inside the nucleus of cells and plays a key role in controlling cell division and cell death. Mutations (changes) in the p53 gene may cause cancer cells to grow and spread in the body.

How does MDM2 cause cancer?

The increased MDM2 levels cause it, in turn, to bind and inactivate p53 by directly blocking the p53 transactivational domain and by targeting the p53 protein for ubiquitin-dependent degradation by the proteasome[72],[73] (Fig. 4).

Is MDM2 a gene?

Mdm2 is a p53 responsive gene—that is, its transcription can be activated by p53. Thus when p53 is stabilized, the transcription of Mdm2 is also induced, resulting in higher Mdm2 protein levels.

How does MDM2 negatively regulate p53?

What is the p53 pathway?

The p53 pathway is composed of a network of genes and their products that are targeted to respond to a variety of intrinsic and extrinsic stress signals that impact upon cellular homeostatic mechanisms that monitor DNA replication, chromosome segregation and cell division (Vogelstein et al., 2000).

What are the two roles of MDM2?

Mdm2 is an important negative regulator of the p53 tumor suppressor. Mdm2 protein functions both as an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain (TAD) of the p53 tumor suppressor and as an inhibitor of p53 transcriptional activation.

What chromosome is MDM2 on?

The MDM2 gene was discovered as one of three genes (MDM1, MDM2, and MDM3) within an amplicon cloned from the tumorigenic mouse cell line 3T3DM (1–3). The genes have different sequences and only MDM2 was found to be amplified in human cancers. In humans, the MDM2 gene (also known as HDM2) is located on chromosome 12q14.

What kind of tumor is amplified by Mdm2?

MDM2 amplified on supernumerary ring or marker chromosomes in many tumors, leading to suppression of p53 Common in atypical lipomatous tumor / well differentiated liposarcoma and dedifferentiated liposarcoma; often used to distinguish these entities from mimickers

Which is oncogene codes for the Mdm2 protein?

Discovery and expression in tumor cells. The murine double minute (mdm2) oncogene, which codes for the Mdm2 protein, was originally cloned, along with two other genes (mdm1 and mdm3) from the transformed mouse cell line 3T3-DM.

How does spindlin 1 inhibit c-mdm2 proto-oncogene?

Spindlin 1 (SPIN1) sequesters ribosomal protein uL18 in the nucleolus, preventing it from interacting with c-mdm2 Proto-oncogene protein (MDM2), and alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity toward p53 tumor suppressor protein (p53).

How does the MDM2 gene affect the risk of osteosarcoma?

The effects of common variants in MDM2 and GNRH2 genes on the risk and survival of osteosarcoma in Han populations from Northwest China. Dysbindin promotes pancreatic ductal adenocarcinoma metastasis by activating NF-kappaB/MDM2 via miR-342-3p. Well-differentiated liposarcoma primary from thymic stroma: Case report and literature review.