Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy.
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.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Autophagy, COVID-19, Cysteine Endopeptidases, Humans, Intracellular Signaling Peptides and Proteins, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Sumoylation, Ubiquitin-Protein Ligases
Angiotensin-Converting Enzyme 2, Autophagy, COVID-19, Cysteine Endopeptidases, Humans, Intracellular Signaling Peptides and Proteins, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Sumoylation, Ubiquitin-Protein Ligases
Nat Commun
Date: Sep. 03, 2022
PubMed ID: 36057605
View in: Pubmed Google Scholar
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