泛素化特异性酶(USP2a)与肿瘤发生的相关分子机制  

Ubiquitin Specific Protease2a(USP2a) Associated with Molecular Mechanism of Tumorigenesis

作　　者：高燕萍[1] 张凯[1] 陈静[1] 李辰[1] 王锐[1] 

机构地区：[1]南京大学附属南京军区南京总医院肿瘤内科,江苏南京210000

出　　处：《现代生物医学进展》2016年第13期2571-2576,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(30901440)

摘　　要：去泛素化酶USP2a是去泛素化酶家族(DUBs)的一个成员,为半胱氨酸蛋白酶,是一种重要的特异性去泛素化水解酶。USP2a具有结构和功能多样性,其结构多样化使得这些酶具有一些特异性作用靶点,特别是在基因表达调控中靶向的生理底物种类繁多。特异性蛋白泛素化水平的动态变化涉及到基因表达活化和失活的多种机制以及信号通路转导的多个环节。越来越多的文献报道了去泛素化酶相互作用网络的组成及其重要性。USP2a调节多种重要的细胞生长和分化调节因子及信号转导因子的稳定性和功能,通过USP2a的去泛素化作用以及诱导它们之间相互反应对机体进行相应调控,特别是在调控转录因子、细胞周期和细胞凋亡自噬上发挥重要作用。USP2a的过表达在体内外都表现出致癌性,其靶蛋白通过各种途径影响肿瘤发生发展。通过对人类肿瘤发生发展的相关分子机制及信号通路影响的深入研究,USP2a有望成为肿瘤治疗的新靶点。现就去泛素化酶与人类肿瘤发生发展的相关分子机制及该领域的研究进展作一综述。USP2a belongs to family of deubiquitination enzymes （DUBs）; as a cysteine protease, it＇s an important specific deu- biquitination hydrolase. Due to its structural and functional diversity, USP2a has some specific targets, especially in the regulation of gene expression possessing a wide variety of targeting physiological substrates. The dynamic change of a level about specific protein ubiquiti- nation n involves not only multiples mechanism underlying the active and inactive of genes expression, but also concerns the transduc- tion of signal pathways. An increasing number of literatures reported to deubiquitin enzyme interaction network composition and its im- portance. USP2a participates in the regulation of cell growth factors, differentiation factors, the stability and function of signal transduc- tion factors. The deubiquitination of USP2a induce the interactions with its target proteins, especially in the regulating transcription fac- tors, cell cycle and apoptosis autophagy. USP2a overexpression in vivo and vitro has shown its carcinogenic, and its target proteins regu- late progression and development of tumors through various pathways. By making further study in human tumor development of the molecular mechanisms and signaling pathways, USP2a is expected to represents a new therapeutic target in tumor. This paper summa- rizes USP2a associated with molecular mechanism of tumorigenesis and the research progress.

关 键 词：去泛素化酶USP2a 肿瘤发生发展 信号通路 分子机制 

分 类 号：R730.231[医药卫生—肿瘤]