p53家族成员在细胞生长、组织发育及肿瘤形成等方面都具有十分重要的生物学功能,其自身受到严格调控,泛素化修饰就是其中非常重要的方式之一,作为泛素化过程中决定底物特异性的泛素连接酶E3作用则更加突出.泛素连接酶E3可以分为两类:RING(really interesting new gene)类和HECT(homologous to E6AP C-terminus)类E3.近年来,HECT类E3对p53家族的调控效应不断得到揭示.本文综述了HECT类E3在调控p53家族转录活性、稳定性方面的重要作用、分子机制以及其作用对生物体肿瘤形成和生长发育等产生的影响,为进一步完善p53家族调控网络,揭示HECT类E3在肿瘤发生发展及防治中的作用提供参考.
p53 family members play very important roles in a variety of biological processes including cell growth, tissue development and tumorigenesis, p53 family are tightly regulated by diverse and complex mechanisms among which ubiquitination as a key member is involved. In the process of ubiquitination, E3 ubiquitin ligases are critical in the recognition of specific substrates. E3s are classified into two major groups: the RING (really interesting new gene) and HECT (homologous to E6AP C-terminus ) types. Recently, increasing evidence have shown that HECT-type E3s were involved in the regulation of p53 family members. In this review, the regulatory role in controlling the transcriptional activity and stability of the p53 family by HECT-type E3s during tumorigenesis and development, and the molecular mechanisms underlying the processes are discussed. We hope that it will be helpful for the further understanding of the p53 regulation network and the HECT E3 contribution to tumor formation and cancer therapy.