title: VIAF, a conserved inhibitor of apoptosis (IAP)-interacting factor that modulates caspase activation.
abstract: Inhibitor of apoptosis (IAP) proteins are involved in the suppression of apoptosis, signal transduction, cell cycle control and gene regulation. Here we describe the cloning and characterization of viral IAP-associated factor (VIAF), a highly conserved, ubiquitously expressed phosphoprotein with limited homology to members of the phosducin family that associates with baculovirus Op-IAP. VIAF bound Op-IAP both in vitro and in intact cells, with each protein displaying a predominantly cytoplasmic localization. VIAF lacks a consensus IAP binding motif, and overexpression of VIAF failed to prevent Op-IAP from protecting human cells from a variety of apoptotic stimuli, suggesting that VIAF does not function as an IAP antagonist. VIAF was unable to directly inhibit caspase activation in vitro and a reduction of VIAF protein levels by RNA interference led to a decrease in Bax-mediated caspase activation, suggesting that VIAF functions to co-regulate the apoptotic cascade. Finally, VIAF is a substrate for ubiquitination mediated by Op-IAP. Thus, VIAF is a novel IAP-interacting factor that functions in caspase activation during apoptosis.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Wilkinson
authors.forename: Bettina W M
authors.initials: BW
authors.lastname: Richter
authors.forename: Amanda S
authors.initials: AS
authors.lastname: Wilkinson
authors.forename: Ezra
authors.initials: E
authors.lastname: Burstein
authors.forename: Julie M
authors.initials: JM
authors.lastname: Rumble
authors.forename: Blerina
authors.initials: B
authors.lastname: Balliu
authors.forename: Colin S
authors.initials: CS
authors.lastname: Duckett
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D016367:Baculoviridae / Q000235:genetics; D001483:Base Sequence; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004789:Enzyme Activation; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009532:Nickel / Q000737:chemistry; D016366:Open Reading Frames; D010750:Phosphoproteins / Q000737:chemistry; D010802:Phylogeny; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions; D014162:Transfection; D020798:Two-Hybrid System Techniques; D025801:Ubiquitin / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics; D051028:bcl-2-Associated X Protein; D009419:Nerve Tissue Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; D020169:Caspases; D018076:DNA, Complementary; D005982:Glutathione Transferase; D049452:Green Fluorescent Proteins; D051034:Inhibitor of Apoptosis Proteins; D009532:Nickel; D010750:Phosphoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D025801:Ubiquitin; D014764:Viral Proteins; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; C498322:PDCL3 protein, human; D009419:Nerve Tissue Proteins