Iwakuma Tomoo, Lozano Guillermina
Section of Cancer Genetics, Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Mol Cancer Res. 2003 Dec;1(14):993-1000.
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.
小鼠双微体2（mdm2）基因编码p53肿瘤抑制因子的负调节因子。mdm2的扩增或通过未知机制导致的表达增加在许多肿瘤中都有发生。因此，MDM2水平的升高会使p53的凋亡和细胞周期阻滞功能失活，就像p53的缺失或突变一样，这是多种肿瘤发生过程中的常见事件。MDM2作为一种E3泛素连接酶可降解p53。MDM2还与另一种肿瘤抑制因子ARF结合。这种相互作用将MDM2隔离在核仁中，使其远离p53，从而激活p53。已经鉴定出许多其他与MDM2相互作用的蛋白质。也已确定了MDM2不依赖于p53的功能。本文介绍了MDM2、其结构和生物学功能，以及它与其结合伙伴的关系。
