Regulation of AR Degradation and Function by Ubiquitylation
Annual rept. 23 Sep 2013-22 Sep 2014
BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
Pagination or Media Count:
Pathways that mediate the ubiquitin dependent degradation of androgen receptor AR remain to be established, and it is apparent that ubiquitylation regulates AR functions in addition to the degradation of unliganded AR. We hypothesize that there are distinct ubiquitin ligases and pathways regulating the degradation and transcriptional functions of liganded nuclear AR versus the unliganded cytoplasmic AR. One of our major objectives is to identify such pathways mediating the turnover of liganded nuclear AR, as these may be exploited therapeutically through the development of selective AR antagonists. Our approach has been to use initially mass spectrometry and identify AR sites that undergo ubiquitylation in the presence and absence of androgen. We have now identified a series of such sites, and current efforts are focused on determining the functional significance of these sites.
- Medicine and Medical Research