Role of the XIAP/AIF Axis in the Development and Progression of Prostate Cancer
Abstract
In the past year tremendous progress has been made towards completing the tasks outlined in the original Statement of Work. The physical association between XIAP and AIF was confirmed in living cells, and it was further determined that XIAP-mediated caspase inhibition was insensitive to AIF over expression. Furthermore, the caspase-inhibitory properties of XIAP were shown to be dispensable for interaction with AIF, and AIF was found to be a substrate of XIAP-mediated ubiquitination. Finally, AIF over expression was determined to result in significant increases in cellular reactive oxygen species levels, and XIAP protein levels are were found to be greatly altered in tissues from Harlequin (AIF deficient) mice. These exciting findings not only confirm the physiological relevance of the association between XIAP and AIF, but also establish a functional link between XIAP and AIF. Importantly, that AIF fails to prevent XIAP-mediated caspase inhibition suggests that the pro-survival NADH-oxidase properties of AIF may play a significant role in tumor formation, despite any death stimulating properties of this protein. Taken together, these observations form the basis for determining the potential role these two proteins play in prostate cancer formation and progression.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2005
- Accession Number
- ADA451361
Entities
People
- John C. Wilkinson
Organizations
- University of Michigan