Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy
© 2022. The Author(s)..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Nature communications - 13(2022), 1 vom: 03. Sept., Seite 5204 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jin, Shouheng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.09.2022 Date Revised 28.03.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-022-32957-y |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM345748298 |
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| 100 | 1 | |a Jin, Shouheng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy |
| 264 | 1 | |c 2022 | |
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| 500 | |a Date Revised 28.03.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Intracellular Signaling Peptides and Proteins |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 650 | 7 | |a TOLLIP protein, human |2 NLM | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
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| 700 | 1 | |a He, Xing |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuang, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yiliang |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Cai, Sihui |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Lu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zheyu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Zhiyao |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yaoxing |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Chunwei |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Weihong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Songyang, Zhou |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Ke |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jincun |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Jun |e verfasserin |4 aut | |
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