Targeted protein degradation in mammalian cells: A promising avenue toward future
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022004433 |
| _version_ | 1797978175469256704 |
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| author | Tianyi Zhang Chuanyang Liu Wenying Li Jingyu Kuang Xin-yuan Qiu Lu Min Lingyun Zhu |
| author_facet | Tianyi Zhang Chuanyang Liu Wenying Li Jingyu Kuang Xin-yuan Qiu Lu Min Lingyun Zhu |
| author_sort | Tianyi Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T05:18:48Z |
| format | Article |
| id | doaj.art-c22079faf9b943aeb0f77684a147e679 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:18:48Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-c22079faf9b943aeb0f77684a147e6792022-12-24T04:54:38ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012054775489Targeted protein degradation in mammalian cells: A promising avenue toward futureTianyi Zhang0Chuanyang Liu1Wenying Li2Jingyu Kuang3Xin-yuan Qiu4Lu Min5Lingyun Zhu6Department of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha, Hunan 410073, ChinaDepartment of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha, Hunan 410073, ChinaDepartment of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha, Hunan 410073, ChinaDepartment of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha, Hunan 410073, ChinaDepartment of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha, Hunan 410073, ChinaDepartment of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha, Hunan 410073, ChinaCorresponding author.; Department of Biology and Chemistry, College of Liberal Arts and Sciences, National University of Defense Technology, Changsha, Hunan 410073, ChinaIn 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.http://www.sciencedirect.com/science/article/pii/S2001037022004433 |
| spellingShingle | Tianyi Zhang Chuanyang Liu Wenying Li Jingyu Kuang Xin-yuan Qiu Lu Min Lingyun Zhu Targeted protein degradation in mammalian cells: A promising avenue toward future Computational and Structural Biotechnology Journal |
| title | Targeted protein degradation in mammalian cells: A promising avenue toward future |
| title_full | Targeted protein degradation in mammalian cells: A promising avenue toward future |
| title_fullStr | Targeted protein degradation in mammalian cells: A promising avenue toward future |
| title_full_unstemmed | Targeted protein degradation in mammalian cells: A promising avenue toward future |
| title_short | Targeted protein degradation in mammalian cells: A promising avenue toward future |
| title_sort | targeted protein degradation in mammalian cells a promising avenue toward future |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022004433 |
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