VIAF, a conserved inhibitor of apoptosis (IAP)-interacting factor that modulates caspase activation.

The Journal of Biological Chemistry
John C WilkinsonColin S Duckett

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.

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Citations

Nov 18, 2008·Chemical Biology & Drug Design·William H BissonMaurizio Pellecchia
Jul 13, 2016·Current Biology : CB·Kay D Bidle
Aug 11, 2018·The Journal of Biological Chemistry·Andrew J ScottJohn C Wilkinson
Oct 27, 2010·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Katarzyna SobierajskaHanna Fabczak
Oct 31, 2007·Molecular and Cellular Biology·John C WilkinsonColin S Duckett
Aug 9, 2016·Journal of Cellular Biochemistry·Łucja Krzemień-OjakHanna Fabczak
Feb 6, 2017·PloS One·Raquel Martín-HernándezNeil Boonham
Dec 12, 2018·Frontiers in Genetics·Kay BoultonAndroniki Psifidi
Jul 31, 2007·Cellular Signalling·Barry M Willardson, Alyson C Howlett

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