Role of the XIAP/AIF Axis in the Development and Progression of Prostate Cancer
Abstract
In the past year significant progress has been made towards completing tasks both outlined in and extending beyond the original Statement of Work. The physical association between XIAP and AIF was determined to be highly dependant upon the ubiquitination status of AIF and XIAP-mediated ubiquitination of AIF was shown not to result in AIF degradation. It was determined that the XIAP antagonist Smac/DIABLO completely disrupted the association between XIAP and AIF in a manner that correlated with an increase in AIF ubiquitination. AIF was determined to be a substrate for cleavage by the serine protease and XIAP antagonist Omi/HtrA2 yet the absence of Omi/HtrA2 did not affect the cytoplasmic release of AIF following apoptosis induction. Interestingly the release of cytochrome c following cell death induction was shown to be delayed in cells deficient in Omi/HtrA2. Finally AIF was found to associate with the XIAP homologues cIAP-1 and cIAP-2 suggesting that AIF may be a general purpose IAP binding protein. These findings represent significant progress in further characterizing the interaction between AIF and the inhibitor of apoptosis (IAP) family and continue to form the basis for understanding how AIF and the IAP family contribute to the pathogenesis of prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2006
- Accession Number
- ADA462873
Entities
People
- John C. Wilkinson
Organizations
- University of Michigan