光诱导人源细胞中的蛋白质降解。

Light-induced protein degradation in human-derived cells.

作者信息

Sun Wansheng, Zhang Wenyao, Zhang Chao, Mao Miaowei, Zhao Yuzheng, Chen Xianjun, Yang Yi

机构信息

Synthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, China; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.

出版信息

Biochem Biophys Res Commun. 2017 May 27;487(2):241-246. doi: 10.1016/j.bbrc.2017.04.041. Epub 2017 Apr 12.

DOI:10.1016/j.bbrc.2017.04.041

PMID:28412349

Abstract

Controlling protein degradation can be a valuable tool for posttranslational regulation of protein abundance to study complex biological systems. In the present study, we designed a light-switchable degron consisting of a light oxygen voltage (LOV) domain of Avena sativa phototropin 1 (AsLOV2) and a C-terminal degron. Our results showed that the light-switchable degron could be used for rapid and specific induction of protein degradation in HEK293 cells by light in a proteasome-dependent manner. Further studies showed that the light-switchable degron could also be utilized to mediate the degradation of secreted Gaussia princeps luciferase (GLuc), demonstrating the adaptability of the light-switchable degron in different types of protein. We suggest that the light-switchable degron offers a robust tool to control protein levels and may serves as a new and significant method for gene- and cell-based therapies.

摘要

控制蛋白质降解可以作为一种有价值的工具，用于对蛋白质丰度进行翻译后调控，以研究复杂的生物系统。在本研究中，我们设计了一种光开关降解子，它由燕麦光敏色素1（AsLOV2）的光氧电压（LOV）结构域和一个C端降解子组成。我们的结果表明，该光开关降解子可用于在HEK293细胞中通过光以蛋白酶体依赖性方式快速、特异性地诱导蛋白质降解。进一步的研究表明，该光开关降解子还可用于介导分泌型海肾荧光素酶（GLuc）的降解，证明了该光开关降解子在不同类型蛋白质中的适应性。我们认为，该光开关降解子为控制蛋白质水平提供了一种强大的工具，并且可能成为基于基因和细胞治疗的一种新的重要方法。