MDMX: from bench to bedside
MDMX: from bench to bedside
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DOI：
10.1242/jcs.03362
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发表时间：
2007-02-01
影响因子：
4
通讯作者：
Jochemsen, Aart G.
中科院分区：
文献类型：
--
作者：
Marine, Jean-Christophe W.;Dyer, Michael A.;Jochemsen, Aart G.
肿瘤抑制蛋白p53受Mdm 2负调控，Mdm 2是靶向p53降解的泛素连接酶蛋白。Mdmx（也称为Mdm 4）是Mdm 2的亲戚，根据其与p53物理相互作用的能力进行鉴定。越来越多的证据，包括最近的遗传学研究，表明Mdmx也是p53的关键负调节因子。因此，MDMX的异常表达可能有助于肿瘤形成。事实上，MDMX扩增和/或过表达发生在几种不同的肿瘤中。引人注目的是，最近的工作将MDMX鉴定为用于治疗视网膜母细胞瘤的特异性化疗靶点。因此，应开发特异性MDMX拮抗剂作为工具，以确保在保留野生型p53的肿瘤中激活“休眠”p53活性。
The tumor suppressor protein p53 is negatively regulated by Mdm2, a ubiquitin ligase protein that targets p53 for degradation. Mdmx (also known as Mdm4) is a relative of Mdm2 that was identified on the basis of its ability to physically interact with p53. An increasing body of evidence, including recent genetic studies, suggests that Mdmx also acts as a key negative regulator of p53. Aberrant expression of MDMX could thus contribute to tumor formation. Indeed, MDMX amplification and/or overexpression occurs in several diverse tumors. Strikingly, recent work identifies MDMX as a specific chemotherapeutic target for treatment of retinoblastoma. Specific MDMX antagonists should therefore be developed as a tool to ensure activation of 'dormant' p53 activity in tumors that retain wild-type p53.