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| Status |
Public on Jul 18, 2022 |
| Title |
SUMOylation restrains the degradation of ACE2 through TOLLIP-mediated selective autophagy to facilitate the host susceptibility to SARS-CoV-2 infection |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Alongside investigations into the virology of SARS-CoV-2, understanding the host–virus dependencies are vital for the identification and rational design of effective antiviral therapy. Here, we report the dominant SARS-CoV-2 entry receptor, ACE2, conjugates with small ubiquitin-like modifier 3 (SUMO3) through a proteome-wide protein interaction analysis. We further demonstrate that 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. Pharmacological intervention of ACE2 SUMOylation blocks the entry of SARS-CoV-2 and viral infection-triggered immune responses. Collectively, our findings suggest selective autophagic degradation of ACE2 orchestrated by SUMOylation and ubiquitination can be targeted to future antiviral therapy of SARS-CoV-2.
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| Overall design |
We analyzed the transcriptome expression of SARS-CoV-2-infected Calu-3 cells with or without 2-D08 treatment, non-treated infection group as control.
We analyzed the transcriptome expression of SARS-CoV-2-infected Calu-3 cells transfected with siNC or siTollip, non-treated infection group as control.
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| Contributor(s) |
Jin S, He X, Ma L, Cui J |
| Citation(s) |
36057605 |
| Submission date |
Mar 30, 2021 |
| Last update date |
Sep 15, 2022 |
| Contact name |
shi jun jie |
| Organization name |
sysu
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| Street address |
zhongshanerlu74hao
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| City |
guangzhou |
| ZIP/Postal code |
471000 |
| Country |
China |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL30209 |
MGISEQ-2000RS (Homo sapiens) |
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| Samples (24)
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| Relations |
| BioProject |
PRJNA718524 |
| SRA |
SRP312714 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE171130_RAW.tar |
6.9 Mb |
(http)(custom) |
TAR (of CSV) |
| GSE171130_reads_count.csv.gz |
5.1 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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