MDM2 oligomers: antagonizers of the guardian of the genome.

MDM2 oligomers: antagonizers of the guardian of the genome.
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MDM2 寡聚物:基因组守护者的拮抗剂。

DOI:
10.1038/onc.2016.88
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发表时间:
2016-12-01
期刊:
影响因子:
8
通讯作者:
Zhang Y
Zhang Y
中科院分区:
医学1区
文献类型:
--
作者:
Leslie PL;Zhang Y

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经过二十年的MDM2研究,我们积累了大量关于MDM2调控和功能的知识,特别是关于其最重要的靶点p53。例如,最近的敲入小鼠研究表明,MDM2异聚物与其同源物MDMX的形成在子宫内抑制p53是必要和充分的,但在成年期则是可有可无的。然而,尽管有这些重要的进展,关于MDM2的基本体内功能的几个方面仍然未知。在一个这样的例子中,尽管大量证据表明MDM2与MDMX形成同源低聚物和异聚物,但这些同源低聚物和异聚物在体内的功能和调控仍不完全清楚。在这篇综述中,我们讨论了目前我们对MDM2寡聚化的认识状况,以及目前针对MDM2寡聚物作为癌症治疗的广泛治疗选择的努力。
Over two decades of MDM2 research has resulted in the accumulation of a wealth of knowledge of many aspects of MDM2 regulation and function, particularly with respect to its most prominent target, p53. For example, recent knock-in mouse studies have shown that MDM2 heterooligomer formation with its homolog, MDMX, is necessary and sufficient in utero to suppress p53 but is dispensable during adulthood. However, despite crucial advances such as these, several aspects regarding basic in vivo functions of MDM2 remain unknown. In one such example, although abundant evidence suggests that MDM2 forms homooligomers and heterooligomers with MDMX, the function and regulation of these homo- and heterooligomers in vivo remain incompletely understood. In this review, we discuss the current state of our knowledge of MDM2 oligomerization as well as current efforts to target the MDM2 oligomer as a broad therapeutic option for cancer treatment.
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