Role of the XIAP-Copper Axis in Prostate Cancer
Annual summary rept. 15 Mar 2008-14 Mar 2010
MICHIGAN UNIV ANN ARBOR
Pagination or Media Count:
During the last two years we have been able to identify, confirm, and characterize a novel functional and physical interaction between the X-linked inhibitor of apoptosis XIAP and the copper chaperone for superoxide dismutase CCS. We performed a targeted genetic screen in yeast to identify proteins involved in delivery of copper Cu to XIAP. This screen identified CCS as a primary mediator of Cu delivery to XIAP in yeast, and we subsequently determined that CCS delivers Cu to XIAP in mammalian cells as well. In addition, XIAP targets CCS for ubiquitination through its E3 ubiquitin ligase activity. This ubiquitination event seems to be proteasome-independent and leads to enhancement of CCS activity rather than CCS degradation. Taken together, our results over the first two years of this project have shed substantial light on the interplay between XIAP and copper homeostasis. These studies have the potential to significantly improve our understanding of not only prostate cancer but also other disorders in which XIAP or Cu metabolism is deregulated.
- Medicine and Medical Research