Figure 2

Molecular determinants of progesterone receptor action. Co-activators/repressors: interactions between PR and known transcriptional co-activators (for example, SRC1) and co-repressors (for example, NCOR/SMRT) are a key determinant of promoter specificity. Pioneer factors: interactions with predicted PR pioneer factors (for example, STAT5, putatively) lead to chromatin remodeling, allowing for efficient PR recruitment and subsequent target-gene transcription. Different pioneer factors would be predicted to determine differential PR recruitment. Post-translational modifications: phosphorylation (P), acetylation (Ac), ubiquitination (Ub), and SUMOylation (Sumo) primarily on N-terminal serine and lysine residues dictate receptor localization, turnover, subcellular localization, and promoter selectivity. Steroid receptor (SR) interactions: emerging evidence suggests that interactions between members of the steroid receptor superfamily (such as ER and PR) determine PR target-gene specificity. Scaffolding interactions: PR interaction with proteins acting as scaffolds (such as DUSP6) determine receptor post-translational modifications, thereby contributing to promoter selection. Cell cycle: phosphorylation on select PR serine residues and cell cycle-dependent protein complex formation determine receptor function and recruitment of PR to specific target genes.