Integrated Program in Cellular, Molecular, and Biomedical Studies, Columbia University, New York, New York 10032, USA.
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Genes Dev. 2021 May 1;35(9-10):575-601. doi: 10.1101/gad.347872.120. Epub 2021 Apr 22.
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.
作为能够抑制抑癌蛋白 p53 的蛋白，MDM2 和 MDMX 受到了广泛的研究。它们与 p53 的关系之外，这两种蛋白还有着丰富的生命活动。我们还有很多东西需要了解，包括这两种蛋白是如何被调控的，以及它们在缺乏 p53 的细胞中是如何发挥功能的。MDM2 和 MDMX 的调控发生在转录、转录后和蛋白质修饰水平，非常复杂，并且依赖于具体的环境。同样复杂的是这两种蛋白在缺乏野生型 p53 的细胞中所扮演的无数角色；虽然这些独立的结果中的许多都与致癌转化一致，但在某些情况下，它们的功能也可能具有肿瘤抑制作用。由于已经开发出许多针对 MDM2 和 MDMX 的小分子药物用于治疗目的，其中大多数（如果不是全部的话）旨在防止它们对 p53 的抑制，因此，了解这些不同的分子可能如何影响 MDM2 和 MDMX 的 p53 非依赖性活性将是至关重要的。
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