LSD1去泛素化酶USP17

摘要

组蛋白去甲基化酶LSD1是一个调控基因表达,影响机体发育和肿瘤发生的重要蛋白,它在细胞内的含量是受到精确调控的,其中LSD1蛋白的泛素化和去泛素化就是重要的调控方式,因此,筛选并研究LSD1的去泛素化修饰酶就显得非常重要.通过蛋白稳定性实验,实时定量PCR,免疫共沉淀,泛素蛋白链检测和信号通路激活实验来鉴定蛋白.通过生长曲线测定来研究基因对细胞增殖的影响.结果显示,USP17能够直接结合LSD1并切除其上的多聚泛素链而稳定LSD1在细胞内的蛋白水平,同时增强LSD1激活的STAT3信号通路,并且促进肿瘤细胞的增殖.因此,USP17是一个LSD1去泛素化酶.%Screen and identify a deubiquitinase of histone demethylase LSD1. Protein stability,real-time quantita-tive PCR, co-immunoprecipitation,ubiquitin chain abolishment and signaling pathway activation assays were ap-plied to identify the enzyme. Cell proliferation assay was applied to study the effects of specific gene on cellular physiology. The data indicate that the deubiquitinase USP17 binds LSD1 directly and removes the ubiquitin chain from it, and so stabilizes the LSD1 protein and enhances its activation of STAT3 signaling pathway. And USP17 promotes cell proliferation through interacting with LSD1. So, USP17 is a deubiquitinase of LSD1.