The SARS-coronavirus membrane protein induces apoptosis via interfering with PDK1-PKB/Akt signalling.
Identifieur interne : 001544 ( Main/Exploration ); précédent : 001543; suivant : 001545The SARS-coronavirus membrane protein induces apoptosis via interfering with PDK1-PKB/Akt signalling.
Auteurs : Ho Tsoi [République populaire de Chine] ; Li Li [République populaire de Chine] ; Zhefan S. Chen [République populaire de Chine] ; Kwok-Fai Lau [République populaire de Chine] ; Stephen K W. Tsui [République populaire de Chine] ; Ho Yin Edwin Chan [République populaire de Chine]Source :
- The Biochemical journal [ 1470-8728 ] ; 2014.
Descripteurs français
- KwdFr :
- Apoptose, Caspases (métabolisme), Cellules HEK293, Humains, Liaison aux protéines, Motifs et domaines d'intéraction protéique, Protein-Serine-Threonine Kinases (métabolisme), Protéines de la matrice virale (), Protéines de la matrice virale (métabolisme), Protéines proto-oncogènes c-akt (métabolisme), Transduction du signal (), Virus du SRAS (métabolisme).
- MESH :
English descriptors
- KwdEn :
- Apoptosis, Caspases (metabolism), HEK293 Cells, Humans, Protein Binding, Protein Interaction Domains and Motifs, Protein-Serine-Threonine Kinases (metabolism), Proto-Oncogene Proteins c-akt (metabolism), Pyruvate Dehydrogenase (Acetyl-Transferring) Kinase, SARS Virus (metabolism), Signal Transduction (drug effects), Viral Matrix Proteins (chemistry), Viral Matrix Proteins (metabolism).
- MESH :
- chemical , chemistry : Viral Matrix Proteins.
- chemical , metabolism : Caspases, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-akt, Viral Matrix Proteins.
- drug effects : Signal Transduction.
- metabolism : SARS Virus.
- Apoptosis, HEK293 Cells, Humans, Protein Binding, Protein Interaction Domains and Motifs, Pyruvate Dehydrogenase (Acetyl-Transferring) Kinase.
Abstract
A number 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.
DOI: 10.1042/BJ20131461
PubMed: 25271362
Affiliations:
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Chen</name><affiliation wicri:level="4"><nlm:affiliation>*Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>*Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Lau, Kwok Fai" sort="Lau, Kwok Fai" uniqKey="Lau K" first="Kwok-Fai" last="Lau">Kwok-Fai Lau</name><affiliation wicri:level="4"><nlm:affiliation>†Biochemistry Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>†Biochemistry Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Tsui, Stephen K W" sort="Tsui, Stephen K W" uniqKey="Tsui S" first="Stephen K W" last="Tsui">Stephen K W. Tsui</name><affiliation wicri:level="4"><nlm:affiliation>║School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>║School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Chan, Ho Yin Edwin" sort="Chan, Ho Yin Edwin" uniqKey="Chan H" first="Ho Yin Edwin" last="Chan">Ho Yin Edwin Chan</name><affiliation wicri:level="4"><nlm:affiliation>*Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>*Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author></analytic><series><title level="j">The Biochemical journal</title><idno type="eISSN">1470-8728</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Apoptosis</term><term>Caspases (metabolism)</term><term>HEK293 Cells</term><term>Humans</term><term>Protein Binding</term><term>Protein Interaction Domains and Motifs</term><term>Protein-Serine-Threonine Kinases (metabolism)</term><term>Proto-Oncogene Proteins c-akt (metabolism)</term><term>Pyruvate Dehydrogenase (Acetyl-Transferring) Kinase</term><term>SARS Virus (metabolism)</term><term>Signal Transduction (drug effects)</term><term>Viral Matrix Proteins (chemistry)</term><term>Viral Matrix Proteins (metabolism)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Apoptose</term><term>Caspases (métabolisme)</term><term>Cellules HEK293</term><term>Humains</term><term>Liaison aux protéines</term><term>Motifs et domaines d'intéraction protéique</term><term>Protein-Serine-Threonine Kinases (métabolisme)</term><term>Protéines de la matrice virale ()</term><term>Protéines de la matrice virale (métabolisme)</term><term>Protéines proto-oncogènes c-akt (métabolisme)</term><term>Transduction du signal ()</term><term>Virus du SRAS (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Viral Matrix Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Caspases</term><term>Protein-Serine-Threonine Kinases</term><term>Proto-Oncogene Proteins c-akt</term><term>Viral Matrix Proteins</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Signal Transduction</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>SARS Virus</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Caspases</term><term>Protein-Serine-Threonine Kinases</term><term>Protéines de la matrice virale</term><term>Protéines proto-oncogènes c-akt</term><term>Virus du SRAS</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Apoptosis</term><term>HEK293 Cells</term><term>Humans</term><term>Protein Binding</term><term>Protein Interaction Domains and Motifs</term><term>Pyruvate Dehydrogenase (Acetyl-Transferring) Kinase</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Apoptose</term><term>Cellules HEK293</term><term>Humains</term><term>Liaison aux protéines</term><term>Motifs et domaines d'intéraction protéique</term><term>Protéines de la matrice virale</term><term>Transduction du signal</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A number 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. </div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country><settlement><li>Sha Tin</li></settlement><orgName><li>Université chinoise de Hong Kong</li></orgName></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Tsoi, Ho" sort="Tsoi, Ho" uniqKey="Tsoi H" first="Ho" last="Tsoi">Ho Tsoi</name></noRegion><name sortKey="Chan, Ho Yin Edwin" sort="Chan, Ho Yin Edwin" uniqKey="Chan H" first="Ho Yin Edwin" last="Chan">Ho Yin Edwin Chan</name><name sortKey="Chen, Zhefan S" sort="Chen, Zhefan S" uniqKey="Chen Z" first="Zhefan S" last="Chen">Zhefan S. Chen</name><name sortKey="Lau, Kwok Fai" sort="Lau, Kwok Fai" uniqKey="Lau K" first="Kwok-Fai" last="Lau">Kwok-Fai Lau</name><name sortKey="Li, Li" sort="Li, Li" uniqKey="Li L" first="Li" last="Li">Li Li</name><name sortKey="Tsui, Stephen K W" sort="Tsui, Stephen K W" uniqKey="Tsui S" first="Stephen K W" last="Tsui">Stephen K W. Tsui</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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