Exploring the Role of Ubiquitination in Progesterone Receptor Transcriptional Activation and Turnover in Breast Cancer Cells

摘要: Abstract : Progesterone Receptors (PR) play important roles in both normal breast development and the progression of cancers. PR action contributes to cell growth survival presence progestins and/or factors. The factor inputs can create receptors with increased transcription response lower concentrations progestins, or hypersensitive ligand. Post-translational modifications such as ubiquitination SUMOylation may be mediating these effects. goal studies is elucidate functional consequences post-translational modifications, specifically, phosphorylationubiquitination on PR, determine temporal relationship between modifications. To accomplish this mutants various phosphorylation sites, conjugation sites consensus sequences have been generated deficient one more Our preliminary data suggests that S294A PR-B has sumoylation relative wt PR-B, whereas unable ubiquitinated. Phosphorylation differentially regulating Transcription reporter assays S294 phosphomimic mutant display heightened indicate SUMO a negative regulator transcriptional activity. by pathways regulates receptor changes hormone responsiveness caner.