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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.