The AUTOTAC chemical biology platform for targeted protein degradation via the autophagy-lysosome system
Seoul National University · Korea Institute of Brain Science · +6 more institutions
Abstract
Abstract Targeted protein degradation allows targeting undruggable proteins for therapeutic applications as well as eliminating proteins of interest for research purposes. While several degraders that harness the proteasome or the lysosome have been developed, a technology that simultaneously degrades targets and accelerates cellular autophagic flux is still missing. In this study, we develop a general chemical tool and platform technology termed AUTOphagy-TArgeting Chimera (AUTOTAC), which employs bifunctional molecules composed of target-binding ligands linked to autophagy-targeting ligands. AUTOTACs bind the ZZ domain of the otherwise dormant autophagy receptor p62/Sequestosome-1/SQSTM1, which is activated…
Citation impact
- FWCI
- 23.56
- Percentile
- 100%
- References
- 43
Authors
22Topics & keywords
- Lysosome
- Autophagy
- Cell biology
- Degradation (telecommunications)
- Protein degradation
- Chemical biology
- Biology
- Computational biology
Funding
- NRNational Research Foundation
- MOMinistry of Science, ICT and Future PlanningAwards: NRF-2020R1A5A1019023, HU21C0201, NRF-2021R1A2B5B03002614, NRF-2021R1A2C3004965, NRF-2016R1A2B3011389, CAP-16-03-KRIBB
- KIKorea Institute of Science and TechnologyAward: 2E31700
- KHKorea Health Industry Development Institute
- KRKorea Research Institute of Bioscience and BiotechnologyAwards: CAP-16-03-KRIBB, CAP-16-03
- NRNational Research Foundation of KoreaAwards: NRF-2021R1A2B5B03002614, 2020R1A5A1019023, 2021R1A2C2093734, NRF-2020R1A5A1019023, 2021R1A2C3004965, 2021R1A2B5B03002614
- NRNational Research Council of Science and TechnologyAward: CAP-16-03-KRIBB
- MOMinistry of Science and ICT, South KoreaAwards: NRF-2021R1A2B5B03002614, 2021R1A2C2093734, NRF-2020R1A5A1019023