The roles and regulation of MDM2 and MDMX: it is not just about p53.
The roles and regulation of MDM2 and MDMX: it is not just about p53.
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DOI：
10.1101/gad.347872.120
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发表时间：
2021-05-01
影响因子：
10.5
通讯作者：
Prives C
中科院分区：
文献类型：
--
作者：
Klein AM;de Queiroz RM;Venkatesh D;Prives C
在这篇综述中，Klein等人讨论了MDM2和MDMX不依赖于p53的作用。首先，他们分别回顾了MDM2和MDMX蛋白的结构和功能特征，这些特征可能与它们不依赖p53的活性有关。在此之后，他们总结了这两种蛋白质是如何被调节的，以及它们如何在缺乏p53的细胞中发挥作用。作为抑制肿瘤抑制蛋白p53的蛋白，MDM2和MDMX在与p53的关系之外有着丰富的生命。关于这两种蛋白质是如何被调节的，以及它们如何在缺乏p53的细胞中发挥作用，还有很多需要了解的。MDM2和MDMX的调控发生在转录、转录后和蛋白质修饰的水平上，可能非常复杂，并且与环境有关。同样复杂的是，这两种蛋白质在缺乏野生型p53的细胞中扮演的无数角色；虽然许多这些独立的结果与致癌转化一致，但在某些情况下，它们的功能也可能是肿瘤抑制。由于许多影响MDM2和MDMX的小分子已被开发用于治疗结果，大多数（如果不是全部的话）被设计用于阻止它们对p53的抑制，因此了解这些不同的分子如何影响MDM2和MDMX的p53非依赖性活性将是至关重要的。
In this review, Klein et al. discuss the p53-independent roles of MDM2 and MDMX. First, they review the structural and functional features of MDM2 and MDMX proteins separately and together that could be relevant to their p53-independent activities. Following this, they summarize how these two proteins are regulated and how they can function in cells that lack p53. Most well studied as proteins that restrain the p53 tumor suppressor protein, MDM2 and MDMX have rich lives outside of their relationship to p53. There is much to learn about how these two proteins are regulated and how they can function in cells that lack p53. Regulation of MDM2 and MDMX, which takes place at the level of transcription, post-transcription, and protein modification, can be very intricate and is context-dependent. Equally complex are the myriad roles that these two proteins play in cells that lack wild-type p53; while many of these independent outcomes are consistent with oncogenic transformation, in some settings their functions could also be tumor suppressive. Since numerous small molecules that affect MDM2 and MDMX have been developed for therapeutic outcomes, most if not all designed to prevent their restraint of p53, it will be essential to understand how these diverse molecules might affect the p53-independent activities of MDM2 and MDMX.
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