Mdm2

Mdm2 is a gene that 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 amplified in a variety of tumor types and mutations in this gene are associated with Li-Fraumeni syndrome, a familial cancer syndrome. Alternative splicing results in multiple transcript variants.

Function

Mdm2 is a key regulator of the p53 tumor suppressor. It is an E3 ubiquitin ligase that recognizes the N-terminal trans-activation domain (TAD) of the p53 tumor suppressor. Mdm2 is also a binding partner of p53 and can inhibit p53-mediated transcriptional activation by binding to its TAD.

Clinical significance

Overexpression of Mdm2 in humans is thought to be a major factor in many types of cancer. In particular, Mdm2 is often amplified in osteosarcoma and glioblastoma. It is also overexpressed in soft tissue sarcomas and in esophageal carcinomas.

Role in cancer

Mdm2 has a central role in the control of cell growth. The overexpression of Mdm2 can inhibit p53, a protein that prevents cell growth and induces apoptosis in the presence of DNA damage. Therefore, overexpression of Mdm2 can lead to uncontrolled cell growth, or cancer.

See also

• p53
• Li-Fraumeni syndrome
• Osteosarcoma
• Glioblastoma

References

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