Regulation of steroid hormone receptors and coregulators during the cell cycle highlights potential novel function in addition to roles as transcription factors

Abstract

Cell cycle progression is tightly controlled by several kinase families including Cyclin-Dependent Kinases, Polo-Like Kinases, and Aurora Kinases. A large amount of data show that steroid hormone receptors and various components of the cell cycle, including cell cycle regulated kinases, interact, and this often results in altered transcriptional activity of the receptor. Furthermore, steroid hormones, through their receptors, can also regulate the transcriptional expression of genes that are required for cell cycle regulation. However, emerging data suggest that steroid hormone receptors may have roles in cell cycle progression independent of their transcriptional activity. The following is a review of how steroid receptors and their coregulators can regulate or be regulated by the cell cycle machinery, with a particular focus on roles independent of transcription in G2/M.

Keywords: cell cycle; kinases; mitosis; phosphorylation; steroid hormone receptors; transcription-independent action.

Figure 1. Steroid receptors and cell cycle regulatory kinases during the cell cycle.

Protein expression (in light blue) and transcriptional activity (in dark blue) of steroid receptors (SRs) and coactivators (ERα, AR, PR, GR and AIB1) during different phases of the cell cycle are shown. During G1/S or S/G2 transition, SR and coactivators generally have high levels of protein expression and transcriptional activities. Both are decreased as the cells progress through G2/M. SRs directly interact with cell cycle kinases (Cyclin D/E/A) to drive G1-S progression. While maintaining the fidelity of cell division, G2/M kinases (PLK1, Aurora A, cyclin B and CDK1, etc.) fine-tune transcriptional levels and protein stability of SRs (ER, AR).