Proteolysis targeting chimera (PROTAC) technology, the recruitment of E3 ubiquitin ligases to induce the degradation of a protein target, is rapidly impacting chemical biology, as well as modern drug development. Here, we explore the universality of this approach by evaluating different E3 ubiquitin ligases, engineered in their substrate binding domains to accept a recruiting ligand. Five out of six E3 ligases were found to be amenable to recruitment for target degradation. Taking advantage of the tight spatiotemporal control of inducing ubiquitination on a preselected target in living cells, we focused on two of the engineered E3 ligases, βTRCP and parkin, to unravel their ubiquitination characteristics in comparison with the PROTAC-recruited endogenous E3 ligases VHL and cereblon.

中文翻译：

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评估不同的E3利加斯用于小分子诱导的蛋白质泛素化和降解

靶向嵌合体的蛋白水解（PROTAC）技术，E3泛素连接酶的募集以诱导蛋白质靶标的降解，正在迅速影响化学生物学以及现代药物的开发。在这里，我们通过评估不同的E3泛素连接酶（在其底物结合域中进行工程改造以接受募集配体）来探索这种方法的普遍性。发现六分之三的E3连接酶适合招募目标降解。利用严格的时空控制在活细胞中预先选择的靶标上诱导泛素化，我们重点研究了两种工程化的E3连接酶βTRCP和parkin，以阐明它们与PROTAC招募的内源性E3连接酶VHL和cereblon相比的泛素化特性。 。