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Article: The SARS-coronavirus membrane protein induces apoptosis via interfering with PDK1PKB/Akt signalling

TitleThe SARS-coronavirus membrane protein induces apoptosis via interfering with PDK1PKB/Akt signalling
Authors
Keywords3-phosphoinositide-dependent protein kinase-1 (PDK1)
Apoptosis
Membrane protein (M-protein)
Protein kinase B (PKB)/Akt
Severe acute respiratory syndrome coronavirus (SARS-CoV)
Issue Date2014
Citation
Biochemical Journal, 2014, v. 464, n. 3, p. 439-447 How to Cite?
AbstractAnumber of viral gene products are capable of inducing apoptosis by interfering with various cellular signalling cascades. We previously reported the pro-apoptotic property of the SARS-CoV (severe acute respiratory syndrome coronavirus) M (membrane)- protein and a down-regulation of the phosphorylation level of the cell-survival protein PKB (protein kinase B)/Akt in cells expressing M-protein. We also showed that overexpression of PDK1 (3-phosphoinositide-dependent protein kinase 1), the immediate upstream kinase of PKB/Akt, suppressed M-induced apoptosis. This illustrates that M-protein perturbs the PDK1 and PKB/Akt cell survival signalling pathway. In the present study, we demonstrated that the C-terminus of M-protein interacts with the PH (pleckstrin homology) domain of PDK1. This interaction disrupted the association between PDK1 and PKB/Akt, and led to down-regulation of PKB/Akt activity. This subsequently reduced the level of the phosphorylated forkhead transcription factor FKHRL1 and ASK (apoptosis signal-regulating kinase), and led to the activation of caspases 8 and 9. Altogether, our data demonstrate that the SARS-CoV M-protein induces apoptosis through disrupting the interaction of PDK1 with PKB/Akt, and this causes the activation of apoptosis. Our work highlights that the SARS-CoV M protein is highly pro-apoptotic and is capable of simultaneously inducing apoptosis via initiating caspases 8 and 9. Preventing the interaction between M-protein and PDK1 is a plausible therapeutic approach to target the pro-apoptotic property of SARS-CoV. The Authors Journal compilation
Persistent Identifierhttp://hdl.handle.net/10722/336131
ISSN
2023 Impact Factor: 4.4
2023 SCImago Journal Rankings: 1.612
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorTsoi, Ho-
dc.contributor.authorLi, Li-
dc.contributor.authorChen, Zhefan S.-
dc.contributor.authorLau, Kwok Fai-
dc.contributor.authorTsui, Stephen K.W.-
dc.contributor.authorChan, Ho Yin Edwin-
dc.date.accessioned2024-01-15T08:23:45Z-
dc.date.available2024-01-15T08:23:45Z-
dc.date.issued2014-
dc.identifier.citationBiochemical Journal, 2014, v. 464, n. 3, p. 439-447-
dc.identifier.issn0264-6021-
dc.identifier.urihttp://hdl.handle.net/10722/336131-
dc.description.abstractAnumber of viral gene products are capable of inducing apoptosis by interfering with various cellular signalling cascades. We previously reported the pro-apoptotic property of the SARS-CoV (severe acute respiratory syndrome coronavirus) M (membrane)- protein and a down-regulation of the phosphorylation level of the cell-survival protein PKB (protein kinase B)/Akt in cells expressing M-protein. We also showed that overexpression of PDK1 (3-phosphoinositide-dependent protein kinase 1), the immediate upstream kinase of PKB/Akt, suppressed M-induced apoptosis. This illustrates that M-protein perturbs the PDK1 and PKB/Akt cell survival signalling pathway. In the present study, we demonstrated that the C-terminus of M-protein interacts with the PH (pleckstrin homology) domain of PDK1. This interaction disrupted the association between PDK1 and PKB/Akt, and led to down-regulation of PKB/Akt activity. This subsequently reduced the level of the phosphorylated forkhead transcription factor FKHRL1 and ASK (apoptosis signal-regulating kinase), and led to the activation of caspases 8 and 9. Altogether, our data demonstrate that the SARS-CoV M-protein induces apoptosis through disrupting the interaction of PDK1 with PKB/Akt, and this causes the activation of apoptosis. Our work highlights that the SARS-CoV M protein is highly pro-apoptotic and is capable of simultaneously inducing apoptosis via initiating caspases 8 and 9. Preventing the interaction between M-protein and PDK1 is a plausible therapeutic approach to target the pro-apoptotic property of SARS-CoV. The Authors Journal compilation-
dc.languageeng-
dc.relation.ispartofBiochemical Journal-
dc.subject3-phosphoinositide-dependent protein kinase-1 (PDK1)-
dc.subjectApoptosis-
dc.subjectMembrane protein (M-protein)-
dc.subjectProtein kinase B (PKB)/Akt-
dc.subjectSevere acute respiratory syndrome coronavirus (SARS-CoV)-
dc.titleThe SARS-coronavirus membrane protein induces apoptosis via interfering with PDK1PKB/Akt signalling-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1042/BJ20131461-
dc.identifier.pmid25271362-
dc.identifier.scopuseid_2-s2.0-84919340841-
dc.identifier.volume464-
dc.identifier.issue3-
dc.identifier.spage439-
dc.identifier.epage447-
dc.identifier.eissn1470-8728-
dc.identifier.isiWOS:000346881700014-

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