期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-32957-y
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资金
- National Key R&D Program of China [2020YFA0908700, 2020YFC0842400]
- National Natural Science Foundation of China [32170876, 31970700, 92042303, 31870862]
- Guangdong Basic and Applied Basic Research Foundation [2020B1515120090]
- Natural Science Foundation of Guangdong Province, China [2021A1515012179]
- Fundamental Research Funds for the Central Universities, Sun Yat-sen University [22qntd2601]
The study found that SARS-CoV-2 infection can modulate the SUMOylation of ACE2, a host receptor used for cell entry, leading to its stabilization and reduced degradation. By inhibiting ACE2 SUMOylation, it is possible to block SARS-CoV-2 infection.
SARS- CoV-2 hijacks ACE2 for cell entry. Here, the authors report that dynamic SUMOylation modulates the TOLLIP-directed selective autophagic degradation of ACE2 and suggest SUMOylation inhibition as a potential intervention against SARS-CoV-2 infection. In addition to investigating the virology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), discovering the host-virus dependencies are essential to identify and design effective antiviral therapy strategy. Here, we report that the SARS-CoV-2 entry receptor, ACE2, conjugates with small ubiquitin-like modifier 3 (SUMO3) and provide evidence indicating that prevention of ACE2 SUMOylation can block SARS-CoV-2 infection. E3 SUMO ligase PIAS4 prompts the SUMOylation and stabilization of ACE2, whereas deSUMOylation enzyme SENP3 reverses this process. Conjugation of SUMO3 with ACE2 at lysine (K) 187 hampers the K48-linked ubiquitination of ACE2, thus suppressing its subsequent cargo receptor TOLLIP-dependent autophagic degradation. TOLLIP deficiency results in the stabilization of ACE2 and elevated SARS-CoV-2 infection. In conclusion, our findings suggest selective autophagic degradation of ACE2 orchestrated by SUMOylation and ubiquitination as a potential way to combat SARS-CoV-2 infection.
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