Shan J, Brooks C, Kon N, Li M, Gu W
Institute for Cancer Genetics and Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University 1130 St. Nicholas Ave, New York, NY 10032, USA.
Ernst Schering Found Symp Proc. 2008(1):127-36. doi: 10.1007/2789_2008_105.
Posttranslational modification of proteins by mono- or polyubiquitination represents a central mechanism to modulate a wide range of cellular functions like protein stability, intracellular transport, protein interactions, and transcriptional activity. Analogous to other posttranslational modifications, ubiquitination is a reversible process counteracted by deubiquitinating enzymes (DUBs), which cleave the isopeptide linkage between protein substrate and the ubiquitin residue. The p53 tumor suppressor is a sequence-specific DNA-binding transcriptional factor that plays a central role in regulating growth arrest and apoptosis during the stress response. Notably, recent studies indicate that both the stability and the subcellular localization of p53 are tightly regulated by ubiquitination; p53 is mainly ubiquitinated by Mdm2 but other ubiquitin ligases such as ARF-BP1/HectH9/MULE are also involved in p53 regulation in vivo. Moreover, a deubiquitinase HAUSP was initially identified in p53 deubiquitination but more recent studies showed that both Mdm2 and Mdmx are also bona fide substrates of HAUSP. In this article, we review our latest understanding of ubiquitination in modulating the p53 tumor suppression pathway.
蛋白质的单泛素化或多泛素化修饰是调节多种细胞功能（如蛋白质稳定性、细胞内运输、蛋白质相互作用和转录活性）的核心机制。与其他翻译后修饰类似，泛素化是一个可逆过程，去泛素化酶（DUBs）可抵消该过程，去泛素化酶能切割蛋白质底物与泛素残基之间的异肽键。p53肿瘤抑制因子是一种序列特异性DNA结合转录因子，在应激反应过程中调节生长停滞和细胞凋亡方面发挥核心作用。值得注意的是，最近的研究表明，p53的稳定性和亚细胞定位均受到泛素化的严格调控；p53主要被Mdm2泛素化，但其他泛素连接酶如ARF-BP1/HectH9/MULE在体内也参与p53的调控。此外，去泛素化酶HAUSP最初是在p53去泛素化过程中被鉴定出来的，但最近的研究表明，Mdm2和Mdmx也是HAUSP的真正底物。在本文中，我们综述了对泛素化调节p53肿瘤抑制途径的最新认识。
