Apoptosis-inducing factor is a target for ubiquitination through interaction with XIAP.
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Wilkinson JC, Wilkinson AS, Galban S, Csomos RA, Duckett CS
Apoptosis-inducing factor is a target for ubiquitination through interaction with XIAP.
Mol Cell Biol. 2008 Jan;28(1):237-47. Epub 2007 Oct 29.
- PubMed ID
- 17967870 [ View in PubMed]
- Abstract
X-linked inhibitor of apoptosis (XIAP) is an inhibitor of apoptotic cell death that protects cells by caspase-dependent and independent mechanisms. In a screen for molecules that participate with XIAP in regulating cellular activities, we identified apoptosis-inducing factor (AIF) as an XIAP binding protein. Baculoviral IAP repeat 2 of XIAP is sufficient for the XIAP/AIF interaction, which is disrupted by Smac/DIABLO. In healthy cells, mature human AIF lacks only the first 54 amino acids, differing significantly from the apoptotic form, which lacks the first 102 amino-terminal residues. Fluorescence complementation and immunoprecipitation experiments revealed that XIAP interacts with both AIF forms. AIF was found to be a target of XIAP-mediated ubiquitination under both normal and apoptotic conditions, and an E3 ubiquitin ligase-deficient XIAP variant displayed a more robust interaction with AIF. Expression of either XIAP or AIF attenuated both basal and antimycin A-stimulated levels of reactive oxygen species (ROS), and when XIAP and AIF were expressed in combination, a cumulative decrease in ROS was observed. These results identify AIF as a new XIAP binding partner and indicate a role for XIAP in regulating cellular ROS.