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The SARS-coronavirus membrane protein induces apoptosis via interfering with PDK1-PKB/Akt signalling

Ho Tsoi1, Li Li1, Zhefan S Chen1

  • 1*Laboratory of Drosophila Research, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China.

The Biochemical Journal
|October 2, 2014
PubMed

Insights

The SARS-CoV M-protein triggers apoptosis by disrupting the PDK1/PKB/Akt survival pathway. This interaction leads to caspase activation, highlighting a therapeutic target for severe acute respiratory syndrome coronavirus infections.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Viral proteins can induce apoptosis by disrupting cellular signaling pathways.
  • The SARS-CoV M-protein exhibits pro-apoptotic properties and downregulates PKB/Akt phosphorylation.
  • Overexpression of PDK1, an upstream kinase of PKB/Akt, suppresses M-protein-induced apoptosis, indicating pathway perturbation.

Purpose of the Study:

  • To elucidate the mechanism by which the SARS-CoV M-protein induces apoptosis.
  • To investigate the interaction between the SARS-CoV M-protein and the PDK1/PKB/Akt signaling pathway.
  • To identify potential therapeutic strategies targeting the M-protein's pro-apoptotic function.

Main Methods:

  • Investigated the interaction between the C-terminus of the SARS-CoV M-protein and the PH domain of PDK1.
  • Assessed the effect of this interaction on the PDK1-PKB/Akt association and PKB/Akt activity.
  • Monitored the phosphorylation levels of FKHRL1 and ASK, and the activation of caspases 8 and 9.

Main Results:

  • Demonstrated that the SARS-CoV M-protein C-terminus interacts with the PDK1 PH domain.
  • Showed this interaction disrupts PDK1-PKB/Akt association, leading to reduced PKB/Akt activity.
  • Observed decreased FKHRL1 and ASK phosphorylation, and subsequent activation of caspases 8 and 9.

Conclusions:

  • The SARS-CoV M-protein induces apoptosis by disrupting the PDK1-PKB/Akt interaction, leading to apoptosis activation.
  • The M-protein is highly pro-apoptotic, activating both caspase 8 and 9 pathways simultaneously.
  • Inhibiting the M-protein-PDK1 interaction presents a potential therapeutic approach against SARS-CoV.

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