VIAF, a conserved inhibitor of apoptosis (IAP)-interacting factor that modulates caspase activation.
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.
Wilkinson
John C
JC
Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Richter
Bettina W M
BW
Wilkinson
Amanda S
AS
Burstein
Ezra
E
Rumble
Julie M
JM
Balliu
Blerina
B
Duckett
Colin S
CS
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
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