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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.

Original publication

DOI

10.1371/journal.ppat.0030017

Type

Journal article

Journal

PLoS Pathog

Publication Date

02/2007

Volume

3

Keywords

Amino Acid Sequence, Animals, Apoptosis, Apoptosis Regulatory Proteins, Cell Line, Tumor, Disease Models, Animal, Eukaryotic Cells, Female, Gene Expression Regulation, Viral, Golgi Apparatus, HeLa Cells, Humans, Membrane Proteins, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Orthopoxvirus, Proteins, Vaccinia, Vaccinia virus, Viral Proteins, Virulence, Virus Replication