TY - JOUR
T1 - VIAF, a conserved inhibitor of apoptosis (IAP)-interacting factor that modulates caspase activation
AU - Wilkinson, John C.
AU - Richter, Bettina W M
AU - Wilkinson, Amanda S.
AU - Burstein, Ezra
AU - Rumble, Julie M.
AU - Balliu, Blerina
AU - Duckett, Colin S.
PY - 2004/12/3
Y1 - 2004/12/3
N2 - 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 pre-dominantly cytoplasmic localization. VIAF lacks a consensus IAP binding motif, and overespression 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.
AB - 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 pre-dominantly cytoplasmic localization. VIAF lacks a consensus IAP binding motif, and overespression 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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U2 - 10.1074/jbc.M409623200
DO - 10.1074/jbc.M409623200
M3 - Article
C2 - 15371430
AN - SCOPUS:10944225049
SN - 0021-9258
VL - 279
SP - 51091
EP - 51099
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 49
ER -