Characterization of a Novel Nuclear Hormone Receptor Coactivator, Uba3, and its Function in Breast Cancer
Annual Summary rept. 1 Mar 2000-28 Feb 2003
BAYLOR COLL OF MEDICINE HOUSTON TX
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We previously identified Uba3 as a nuclear hormone receptor coactivator that functions as part of the NEDD8 pathway to influence ER- and PR-mediated transcription. Although our previous model failed to demonstrate the connection between Uba3, the NEDD8 pathway, and transcription, we now have sufficient evidence to suggest the NEDD8 pathway is linked to ER- and PR-mediated transcription via the SCF E3 ligase complex. Here we show that Skpl can associate with ERalpha by co-immunoprecipitation, and with the p52 promoter by ChIP assay. We have investigated the mRNA expression of Uba3, PR, and ERa in several common tumor cell lines. We were not able to detect abnormal expression of huba3 mRNA in the breast cancer cell lines. Furthermore, we were unable to correlate hUba3 mRNA expression with PR and ERalpha expression across all cell lines. We also investigated in silico the potential that Uba3 mRNA expression may be regulated by estrogen and progesterone. Although possible binding sites for ER and PR were localized within the Uba3 promoter, we were not able to detect induction or repression of Uba3 mRNA by estradiol, and SERMs tamoxifen, and raloxifene, or progesterone.
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