A new inhibitor of apoptosis from vaccinia virus and eukaryotes.
A new apoptosis inhibitor is described from vaccinia virus, camelpox virus, and eukaryotic cells. The inhibitor is a hydrophobic, multiple transmembrane protein that is resident in the Golgi and is named GAAP (Golgi anti-apoptotic protein). Stable expression of both viral GAAP (v-GAAP) and human GAAP (h-GAAP), which is expressed in all human tissues tested, inhibited apoptosis induced by intrinsic and extrinsic apoptotic stimuli. Conversely, knockout of h-GAAP by siRNA induced cell death by apoptosis. v-GAAP and h-GAAP display overlapping functions as shown by the ability of v-GAAP to complement for the loss of h-GAAP. Lastly, deletion of the v-GAAP gene from vaccinia virus did not affect virus replication in cell culture, but affected virus virulence in a murine infection model. This study identifies a new regulator of cell death that is highly conserved in evolution from plants to insects, amphibians, mammals, and poxviruses.
Gubser
Caroline
C
Department of Virology, Faculty of Medicine, Imperial College London, London, United Kingdom. c.gubser@imperial.ac.uk
Bergamaschi
Daniele
D
Hollinshead
Michael
M
Lu
Xin
X
van Kuppeveld
Frank J M
FJ
Smith
Geoffrey L
GL
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005057:Eukaryotic Cells / Q000378:metabolism*; D005260:Female; D015967:Gene Expression Regulation, Viral; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018155:Orthopoxvirus / Q000378:metabolism* / Q000472:pathogenicity; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014615:Vaccinia / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D014616:Vaccinia virus / Q000378:metabolism* / Q000472:pathogenicity; D014764:Viral Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014774:Virulence; D014779:Virus Replication / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; C518282:GAAP protein, vaccinia virus; D008565:Membrane Proteins; D011506:Proteins; C518281:TMBIM4 protein, human; D014764:Viral Proteins