Alarcon-Vargas Dania, Ronai Ze'ev
Ruttenberg Cancer Center Mount Sinai School of Medicine, New York, NY 10029, USA.
Carcinogenesis. 2002 Apr;23(4):541-7. doi: 10.1093/carcin/23.4.541.
The p53-Mdm2 paradigm represents the best-studied relationship between a tumor suppressor gene which functions as a transcription factor and an oncogene, which functions primarily as an E3 protein ligase. The intimate relationship between these two partners has expanded to include almost every cellular biological system - from development, to growth control and programmed cell death. The affair between Mdm2 and p53 is closely controlled by a complex array of post-translational modifications, which in turn dictates the stability and activity of p53 and Mdm2. Functional diversity depends on the association with a large subset of partner proteins, which dictates the type of activity and corresponding selectivity. Here we summarize the current understanding of post-translational modifications and their effect on conformation-based functional relationship between Mdm2 and p53, as it pertains to their diverse cellular biological functions.
p53-Mdm2范式代表了作为转录因子的肿瘤抑制基因与主要作为E3蛋白连接酶发挥作用的癌基因之间研究最为深入的关系。这两个伙伴之间的密切关系已扩展到几乎每一个细胞生物学系统——从发育到生长控制和程序性细胞死亡。Mdm2和p53之间的关系受到一系列复杂的翻译后修饰的严格控制，这些修饰反过来又决定了p53和Mdm2的稳定性和活性。功能多样性取决于与大量伙伴蛋白的结合，这决定了活性类型和相应的选择性。在这里，我们总结了目前对翻译后修饰及其对Mdm2和p53之间基于构象的功能关系的影响的理解，因为这与它们多样的细胞生物学功能相关。
