Chemical ubiquitination for decrypting a cellular code.
Chemical ubiquitination for decrypting a cellular code.
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DOI：
10.1042/bj20151195
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发表时间：
2016-05-15
期刊：
影响因子：
--
通讯作者：
Virdee S
中科院分区：
文献类型：
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作者：
Stanley M;Virdee S
泛素（ubiquitin，Ub）对蛋白质的修饰是真核生物学的一个重要调节因子，而这一过程的有害干扰与多种疾病的发生密切相关。Ub信号的调节能力很高，部分原因是Ub能够被酶促聚合形成八种不同连接类型的聚泛蛋白（polyUb）链。然后，这些不同的polyUb拓扑结构可以与底物蛋白位点特异性缀合，以引发许多细胞结果。因此，为了进一步阐明底物泛素化的生物学意义，允许产生定义的polyUb种类的方法，以及用它们进行位点特异性修饰的底物蛋白，对于我们的理解是必不可少的。最近出现了许多受化学启发的方法，这些方法满足了深入了解UB生物学所必需的许多标准。为了在传统的生物学研究实验室提供直接的影响，本综述的目的是提供一个概述的技术，可用于制备Ub缀合物和polyUb链，重点是使用重组蛋白构建块的方法。这些方法产生天然异肽或其类似物，其可以被去泛素酶水解或不可水解。最重要的生物学的见解，已经收集使用这种方法也将被总结。
The modification of proteins with ubiquitin (Ub) is an important regulator of eukaryotic biology and deleterious perturbation of this process is widely linked to the onset of various diseases. The regulatory capacity of the Ub signal is high and, in part, arises from the capability of Ub to be enzymatically polymerised to form polyubiquitin (polyUb) chains of eight different linkage types. These distinct polyUb topologies can then be site-specifically conjugated to substrate proteins to elicit a number of cellular outcomes. Therefore, to further elucidate the biological significance of substrate ubiquitination, methodologies that allow the production of defined polyUb species, and substrate proteins that are site-specifically modified with them, are essential to progress our understanding. Many chemically inspired methods have recently emerged which fulfil many of the criteria necessary for achieving deeper insight into Ub biology. With a view to providing immediate impact in traditional biology research labs, the aim of this review is to provide an overview of the techniques that are available for preparing Ub conjugates and polyUb chains with focus on approaches that use recombinant protein building blocks. These approaches either produce a native isopeptide, or analogue thereof, that can be hydrolysable or non-hydrolysable by deubiquitinases. The most significant biological insights that have already been garnered using such approaches will also be summarized.