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机构地区:[1]北京林业大学理学院,北京100083 [2]北京师范大学生命科学学院,细胞增殖及调控生物学教育部重点实验室,北京100875
出 处:《生物化学与生物物理进展》2011年第12期1091-1098,共8页Progress In Biochemistry and Biophysics
基 金:国家自然科学基金资助项目(30770030,31070714);北京市科技新星计划资助项目(2005B47)~~
摘 要:真核泛素-蛋白酶体系统是细胞内蛋白质降解的重要机制,参与细胞生理功能调控,因此泛素-蛋白酶体通路的机制和功能研究备受关注.20世纪80年代,人们就发现放线菌中存在原核蛋白酶体,但是对于原核蛋白酶体的功能和作用机理长期以来了解甚少.2008年,Pearce等在结核分枝杆菌中发现了原核类泛素蛋白(prokaryotic ubiquitin-like protein,Pup).在Dop、PafA、Mpa等辅助因子的作用下,Pup可以共价标记多种功能蛋白,并介导被标记蛋白质通过蛋白酶体降解,Pup-蛋白酶体系统的发现揭示了原核生物中一个崭新的蛋白质降解机制.Pup-蛋白酶体系统的靶蛋白涉及物质中间代谢、信号通路、毒性和抗毒性因子、细胞壁和细胞膜组分等多个方面,并且与结核分枝杆菌的致病性相关,被认为是新的结核病治疗药物靶点.本文就原核Pup-蛋白酶体系统的作用机理及其功能的研究进展作一综述.Ubiquitin-proteasome system,the essential mechanism for eukaryotic cellular protein degradation, plays an important role in the regulation of cellular physiological functions.In 1980s,researchers found that proteasome also reside in actinomycetes,but the function and mechanism of the prokaryotic proteasome were unknown.In 2008,the prokaryotic ubiquitin-like protein(Pup) was identified in Mycobacterium tuberculosis.With the help of accessory factors,Dop,PafA and Mpa,Pup covalently linked to the Lys ε-NH2 in the target proteins and mediated the target protein degradation through the proteasome.The discovery of Pup-proteasome system revealed a novel mechanism of prokaryotic protein degradation,which is involved essential physiological function including the intermediary metabolism,information pathway,detoxification/virulence,cell wall and cell membrane formation and so on.Disruption of Pup-proteasome system can suppress the pathogenicity of Mycobacterium tuberculosis.Therefore it is regarded as the new therapeutic target for tuberculosis.In the present paper,the progress in the study on mechanism and function of Pup-proteasome system is reviewed.
关 键 词:原核类泛素蛋白(Pup) 蛋白酶体 蛋白质降解 结核分枝杆菌
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