泛素
泛素连接酶
细胞生物学
溶酶体
泛素结合酶
脱氮酶
内体
内吞循环
内吞作用
蛋白质靶向
生物
F盒蛋白
网格蛋白
泛素蛋白连接酶类
生物化学
整体膜蛋白
化学
液泡蛋白分选
逆转体
分类
排序nexin
ESCRT公司
膜蛋白
受体
基因
膜
酶
细胞内
出处
期刊:Essays in Biochemistry
[Portland Press]
日期:2005-10-01
卷期号:41 (1): 81-81
被引量:47
摘要
Ubiquitin plays a fundamental role not only in proteasome-mediated protein degradation but also in the targeting of membrane proteins for degradation inside the lysosome. Ubiquitination provides a key signal for endosomal sorting of membrane proteins into the MVB (multi-vesicular body), which delivers its cargo to the proteolytic interior of the lysosome. Attachment of single ubiquitin molecules, rather than ubiquitin chains, to one or multiple lysines of the cytoplasmic domains of many growth factor receptors, ion channels and other membrane transporters is sufficient to target these proteins to a complex sorting apparatus on the endosome. This machinery selects ubiquitinated proteins for lysosomal sorting through consecutive interactions with a variety of ubiquitin-binding domains. The major ubiquitin ligase (E3) responsible for ubiquitination in this pathway in yeast is the HECT [homologous to E6-AP (E6-associated protein) C-terminus]-ligase, Rsp5, whereas in mammalian cells the RING (really interesting new gene)-ligase Cbl has been implicated in the down-regulation of several RTKs (receptor tyrosine kinases). Ubiquitinated receptors can be rescued from degradation by the activity of DUBs (deubiquitinating enzymes), which may provide a proofreading mechanism that enhances the fidelity of this sorting and degradation process. DUBs also allow for recycling of the ubiquitin moieties from proteins prior to their final commitment to the MVB and lysosome interior.
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