ACE2 in chronic disease and COVID-19: gene regulation and post-translational modification.
ACE2
Angiotensin II
COVID-19
Chronic disease
Glycosylation
Phosphorylation
SARS-CoV-2
Transcription
Ubiquitination
Journal
Journal of biomedical science
ISSN: 1423-0127
Titre abrégé: J Biomed Sci
Pays: England
ID NLM: 9421567
Informations de publication
Date de publication:
22 Aug 2023
22 Aug 2023
Historique:
received:
06
06
2023
accepted:
15
08
2023
medline:
24
8
2023
pubmed:
23
8
2023
entrez:
23
8
2023
Statut:
epublish
Résumé
Angiotensin-converting enzyme 2 (ACE2), a counter regulator of the renin-angiotensin system, provides protection against several chronic diseases. Besides chronic diseases, ACE2 is the host receptor for SARS-CoV or SARS-CoV-2 virus, mediating the first step of virus infection. ACE2 levels are regulated by transcriptional, post-transcriptional, and post-translational regulation or modification. ACE2 transcription is enhanced by transcription factors including Ikaros, HNFs, GATA6, STAT3 or SIRT1, whereas ACE2 transcription is reduced by the transcription factor Brg1-FoxM1 complex or ERRα. ACE2 levels are also regulated by histone modification or miRNA-induced destabilization. The protein kinase AMPK, CK1α, or MAP4K3 phosphorylates ACE2 protein and induces ACE2 protein levels by decreasing its ubiquitination. The ubiquitination of ACE2 is induced by the E3 ubiquitin ligase MDM2 or UBR4 and decreased by the deubiquitinase UCHL1 or USP50. ACE2 protein levels are also increased by the E3 ligase PIAS4-mediated SUMOylation or the methyltransferase PRMT5-mediated ACE2 methylation, whereas ACE2 protein levels are decreased by AP2-mediated lysosomal degradation. ACE2 is downregulated in several human chronic diseases like diabetes, hypertension, or lung injury. In contrast, SARS-CoV-2 upregulates ACE2 levels, enhancing host cell susceptibility to virus infection. Moreover, soluble ACE2 protein and exosomal ACE2 protein facilitate SARS-CoV-2 infection into host cells. In this review, we summarize the gene regulation and post-translational modification of ACE2 in chronic disease and COVID-19. Understanding the regulation and modification of ACE2 may help to develop prevention or treatment strategies for ACE2-mediated diseases.
Identifiants
pubmed: 37608279
doi: 10.1186/s12929-023-00965-9
pii: 10.1186/s12929-023-00965-9
pmc: PMC10464117
doi:
Substances chimiques
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
MAP4K3 protein, human
EC 2.7.11.1
PRMT5 protein, human
EC 2.1.1.319
Protein Serine-Threonine Kinases
EC 2.7.11.1
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
ACE2 protein, human
EC 3.4.17.23
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
71Subventions
Organisme : National Health Research Institutes
ID : IM-112-SP-01
Organisme : National Science and Technology Council
ID : NSTC-111-2320-B-400-003
Informations de copyright
© 2023. National Science Council of the Republic of China (Taiwan).
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