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1 Section of Cancer Genetics, Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, TX
Requests for reprints: Guillermina Lozano, Section of Cancer Genetics, Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, Unit 11, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: (713) 792-8945; Fax: (713) 792-8382. E-mail: gglozano{at}mdanderson.org
Abstract
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. Thus, increased levels of MDM2 would inactivate the apoptotic and cell cycle arrest functions of p53, as do deletion or mutation of p53, common events in the genesis of many kinds of tumors. MDM2 functions as an E3 ubiquitin ligase to degrade p53. MDM2 also binds another tumor suppressor, ARF. This interaction sequesters MDM2 in the nucleolus away from p53, thus activating p53. Many additional MDM2 interacting proteins have been identified. Functions of MDM2 independent of p53 have also been identified. This article is an introduction to MDM2, its structure and biological functions, as well as its relationship to its binding partners.
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