A new inhibitor of apoptosis from vaccinia virus and eukaryotes

PLoS Pathog. 2007 Feb;3(2):e17. doi: 10.1371/journal.ppat.0030017.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins / analysis
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Eukaryotic Cells / metabolism*
  • Female
  • Gene Expression Regulation, Viral
  • Golgi Apparatus / metabolism*
  • HeLa Cells
  • Humans
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Orthopoxvirus / metabolism*
  • Orthopoxvirus / pathogenicity
  • Proteins / analysis
  • Proteins / genetics
  • Proteins / metabolism
  • Vaccinia / metabolism
  • Vaccinia / physiopathology
  • Vaccinia / virology
  • Vaccinia virus / metabolism*
  • Vaccinia virus / pathogenicity
  • Viral Proteins / analysis
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virulence
  • Virus Replication / physiology


  • Apoptosis Regulatory Proteins
  • GAAP protein, vaccinia virus
  • Membrane Proteins
  • Proteins
  • TMBIM4 protein, human
  • Viral Proteins

Associated data

  • GENBANK/AAD34114
  • GENBANK/AAF14868
  • GENBANK/AAG37461
  • GENBANK/AAH90219
  • GENBANK/AF182041
  • GENBANK/AY690669
  • GENBANK/AY699305
  • GENBANK/AY699306