a new inhibitor of apoptosis from vaccinia virus and eukaryotes一个新的抑制剂牛痘病毒的细胞凋亡和真核生物.pdfVIP

A New Inhibitor of Apoptosis from Vaccinia Virus and Eukaryotes 1* 2¤ 1 2 3 Caroline Gubser , Daniele Bergamaschi , Michael Hollinshead , Xin Lu , Frank J. M. van Kuppeveld , 1* Geoffrey L. Smith 1 Department of Virology, Faculty of Medicine, Imperial College London, London, United Kingdom, 2 Ludwig Institute for Cancer Research, Faculty of Medicine, Imperial College London, London, United Kingdom, 3 Department of Medical Microbiology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands 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. Citation: Gubser C, Bergamaschi D, Hollinshead M, Lu X, van Kuppeveld FJM, et al. (2007) A new inhibitor of apoptosis from vaccinia virus and eukaryotes. PLoS Pathog 3(2): e17. doi:10.1371/journal.ppat.0030017 Introduction