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.
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Research Article|
December 05 2014
The SARS-coronavirus membrane protein induces apoptosis via interfering with PDK1–PKB/Akt signalling
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Ho Tsoi;
Ho Tsoi
*Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
†Biochemistry Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
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Li Li;
Li Li
*Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
†Biochemistry Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
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Zhefan S. Chen;
Zhefan S. Chen
*Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
†Biochemistry Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
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Kwok-Fai Lau;
Kwok-Fai Lau
†Biochemistry Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
‡Cell and Molecular Biology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
§Molecular Biotechnology Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
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Stephen K. W. Tsui;
Stephen K. W. Tsui
║School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
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Ho Yin Edwin Chan
Ho Yin Edwin Chan
1
*Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
†Biochemistry Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
‡Cell and Molecular Biology Programme, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
§Molecular Biotechnology Programme, School of Life Sciences, Faculty of Science, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China
1To whom correspondence should be addressed (email hyechan@cuhk.edu.hk).
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Publisher: Portland Press Ltd
Received:
November 04 2013
Revision Received:
September 22 2014
Accepted:
October 01 2014
Accepted Manuscript online:
October 01 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2014 Biochemical Society
2014
Biochem J (2014) 464 (3): 439–447.
Article history
Received:
November 04 2013
Revision Received:
September 22 2014
Accepted:
October 01 2014
Accepted Manuscript online:
October 01 2014
Citation
Ho Tsoi, Li Li, Zhefan S. Chen, Kwok-Fai Lau, Stephen K. W. Tsui, Ho Yin Edwin Chan; The SARS-coronavirus membrane protein induces apoptosis via interfering with PDK1–PKB/Akt signalling. Biochem J 15 December 2014; 464 (3): 439–447. doi: https://doi.org/10.1042/BJ20131461
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