Fåhraeus R, Olivares-Illana V
Cibles Therapeutiques, Equipe Labellisée Ligue Contre le Cancer, INSERM Unité 940, Institut de Génétique Moléculaire, Université Paris 7, Hôpital St Louis, 27 rue Juliette Dodu, Paris, France.
Instituto de Física, Universidad Autónoma de San Luis Potosí, Av. Manuel Nava, Zona Universitaria, San Luis Potosí, México.
Oncogene. 2014 Aug 28;33(35):4365-76. doi: 10.1038/onc.2013.410. Epub 2013 Oct 7.
MDM2 is considered a hub protein due to its capacity to interact with a large number of different partners of which p53 is most well described. MDM2 is an E3 ubiquitin ligase, and many, but not all, of its interactions relate directly to this activity, such as substrates, adaptors or bridges, promoters, inhibitors or complementary factors. Some interactions serve regulatory functions that in response to cellular stresses control the localisation and functions of MDM2 including protein kinases, ribosomal proteins and proteases. Moreover, interactions with nucleotides serve other functions such as mRNA to regulate protein synthesis and DNA to control transcription. To perform such a pleiotropic panorama of different functions, MDM2 is subjected to a multitude of post-translational modifications and is expressed in different isoforms. The large and diverse interactome is made possible due to the plasticity of MDM2 and in this review we have listed the MDM2 interactions until now and we will discuss how this multifaceted protein can interact with such a variety of substrates to provide a key intermediary role in different signalling pathways.
MDM2被认为是一种枢纽蛋白,因为它能够与大量不同的蛋白相互作用,其中对p53的描述最为详尽。MDM2是一种E3泛素连接酶,其许多(但并非全部)相互作用都直接与此活性相关,例如底物、衔接蛋白或桥梁蛋白、启动子、抑制剂或互补因子。一些相互作用具有调节功能,可响应细胞应激控制MDM2的定位和功能,包括蛋白激酶、核糖体蛋白和蛋白酶。此外,与核苷酸的相互作用具有其他功能,如mRNA用于调节蛋白质合成,DNA用于控制转录。为了实现如此多不同功能的全景展示,MDM2会经历多种翻译后修饰,并以不同的异构体形式表达。由于MDM2的可塑性,才形成了庞大且多样的相互作用组,在本综述中,我们列出了迄今为止MDM2的相互作用,并将讨论这种多面蛋白如何与如此多样的底物相互作用,从而在不同的信号通路中发挥关键的中介作用。