The SARS-Coronavirus Membrane protein induces apoptosis through modulating the Akt survival pathway.
A number of viral gene products are capable of triggering apoptotic cell death through interfering with cellular signaling cascades, including the Akt kinase pathway. In this study, the pro-apoptotic role of the SARS-CoV Membrane (M) structural protein is described. We found that the SARS-CoV M protein induced apoptosis in both HEK293T cells and transgenic Drosophila. We further showed that M protein-induced apoptosis involved mitochondrial release of cytochrome c protein, and could be suppressed by caspase inhibitors. Over-expression of M caused a dominant rough-eye phenotype in adult Drosophila. By performing a forward genetic modifier screen, we identified phosphoinositide-dependent kinase-1 (PDK-1) as a dominant suppressor of M-induced apoptotic cell death. Both PDK-1 and Akt kinases play essential roles in the cell survival signaling pathway. Altogether, our data show that SARS-CoV M protein induces apoptosis through the modulation of the cellular Akt pro-survival pathway and mitochondrial cytochrome c release.
Chan
Chak-Ming
CM
Laboratory of Drosophila Research, Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Ma
Cheuk-Wing
CW
Chan
Wood-Yee
WY
Chan
Ho Yin Edwin
HY
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival; D000086862:Coronavirus M Proteins; D004330:Drosophila; D006801:Humans; D007668:Kidney / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D010766:Phosphorylation; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism*
D000086862:Coronavirus M Proteins; C000706237:M protein, SARS-CoV; D014763:Viral Matrix Proteins; D051058:Oncogene Protein v-akt