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Regulation of membrane protein transport by ubiquitin and ubiquitin-binding proteins.
Annual Review of Cell and Developmental Biology ( IF 11.4 ) Pub Date : 2003-10-23 , DOI: 10.1146/annurev.cellbio.19.110701.154617
Linda Hicke 1 , Rebecca Dunn
Affiliation  

Ubiquitin regulates protein transport between membrane compartments by serving as a sorting signal on protein cargo and by controlling the activity of trafficking machinery. Monoubiquitin attached to integral plasma membrane proteins or to associated transport modifiers serves as a regulated signal for internalization into the endocytic pathway. Similarly, monoubiquitin attached to biosynthetic and endocytic membrane proteins is a signal for sorting of cargo into vesicles that bud into the late endosome lumen for delivery into the lysosome. Ubiquitination of trans-acting endocytic proteins is also required for transport, and key endocytic proteins are modified by monoubiquitin. Regulatory enzymes of the ubiquitination machinery, ubiquitin ligases, control the timing and specificity of plasma membrane protein downregulation in such diverse biological processes as cell fate specification and neurotransmission. Monoubiquitin signals appended by these ligases are recognized by endocytic proteins carrying ubiquitin-binding motifs, including UBA, UEV, UIM, and CUE domains. The UIM proteins epsins and Hrs are excellent candidates for adaptors that link ubiquitinated cargo to the clathrin-based sorting machinery at appropriate regions of the endosomal or plasma membranes. Other ubiquitin-binding proteins also play crucial roles in cargo transport, although in most cases the role of ubiquitin-binding is not defined. Ubiquitin-binding proteins such as epsins, Hrs, and Vps9 are monoubiquitinated, indicating the general nature of ubiquitin regulation in endocytosis and suggesting new models to explain how recognition of monoubiquitin signals may be regulated.

中文翻译:

调节遍在蛋白和遍在蛋白结合蛋白的膜蛋白。

泛素通过充当蛋白质货物上的分类信号并控制运输机械的活动来调节膜区室之间的蛋白质运输。附着于完整质膜蛋白或相关转运修饰物的单泛素充当内化进入内吞途径的调节信号。同样,附着在生物合成和内吞膜蛋白上的单泛素是将货物分拣到囊泡中的信号,这些囊泡发芽进入晚期的内体腔,然后传递到溶酶体中。反式作用内吞蛋白的泛素化也是运输所必需的,关键的内吞蛋白被单泛素修饰。泛素化机制的调节酶,泛素连接酶,在诸如细胞命运指定和神经传递等多种生物过程中控制质膜蛋白下调的时机和特异性。这些连接酶附加的单泛素信号被带有泛素结合基序的内吞蛋白识别,包括UBA,UEV,UIM和CUE域。UIM蛋白epsins和Hrs是衔接子的极佳候选者,这些衔接子将遍在蛋白的货物与内体或质膜适当区域的基于网格蛋白的分选机制相连接。其他泛素结合蛋白在货物运输中也起着至关重要的作用,尽管在大多数情况下,泛素结合的作用尚未定义。泛素结合蛋白(例如epsins,Hrs和Vps9)被单泛素化,
更新日期:2019-11-01
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