Targeted protein degradation in mammalian cells: A promising avenue toward future.
Targeted protein degradation in mammalian cells: A promising avenue toward future.
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哺乳动物细胞中的靶向蛋白质降解：通向未来的有希望的途径
DOI：
10.1016/j.csbj.2022.09.038
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发表时间：
2022
影响因子：
6
通讯作者：
Zhu, Lingyun
中科院分区：
文献类型：
--
作者：
Zhang, Tianyi;Liu, Chuanyang;Li, Wenying;Kuang, Jingyu;Qiu, Xin-yuan;Min, Lu;Zhu, Lingyun
在真核细胞环境中，蛋白质通过内源性蛋白质降解机制如泛素-蛋白酶体和溶酶体途径持续合成和有效降解。通过重新设计和重新利用这些天然蛋白质调控机制，靶向蛋白质降解（TPD）策略为生物学家提供了强大的工具，可以在翻译后水平直接，精确和可逆地操纵感兴趣的蛋白质的丰度。近年来，TPD得到了广泛的关注，并被认为是基础研究，应用导向的合成生物学和开创性临床工作的范式转变。本文综述了目前最先进的TPD技术，如Trim-Away、LYTAC和AUTAC的最新信息，特别是工程方面的努力和发展路线。此外，还分析了TPD技术的设计原则、优点、存在的问题以及有待解决的问题，以期为今后新型TPD技术的探索、发现和进一步应用提供指导。
In the eukaryotic cellular milieu, proteins are continuously synthesized and degraded effectively via endogenous protein degradation machineries such as the ubiquitin–proteasome and lysosome pathways. By reengineering and repurposing these natural protein regulatory mechanisms, the targeted protein degradation (TPD) strategies are presenting biologists with powerful tools to manipulate the abundance of proteins of interest directly, precisely, and reversibly at the post-translational level. In recent years, TPD is gaining massive attention and is recognized as a paradigm shift both in basic research, application-oriented synthetic biology, and pioneering clinical work. In this review, we summarize the updated information, especially the engineering efforts and developmental route, of current state-of-the-art TPD technology such as Trim-Away, LYTACs, and AUTACs. Besides, the general design principle, benefits, problems, and opportunities to be addressed were further analyzed, with the aim of providing guidelines for exploration, discovery, and further application of novel TPD tools in the future.
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影响因子：
11.2
作者：
Chen, W;Lee, JW;Fine, HA
通讯作者：
Fine, HA
Parkin对泛素 - 蛋白酶体系统的广泛激活对于线粒体至关重要。
影响因子：
3.5
作者：
Chan NC;Salazar AM;Pham AH;Sweredoski MJ;Kolawa NJ;Graham RL;Hess S;Chan DC
通讯作者：
Chan DC
影响因子：
64.8
作者：
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通讯作者：
Bertozzi CR
影响因子：
4
作者：
Bonger, Kimberly M.;Rakhit, Rishi;Payumo, Alexander Y.;Chen, James K.;Wandless, Thomas J.
通讯作者：
Wandless, Thomas J.
影响因子：
16
作者：
Bennett, EJ;Bence, NF;Kopito, RR
通讯作者：
Kopito, RR