Figure 7. Myosin phosphatase is a dynamic ligand-independent regulator of AR function.

Schematic summary of MLCP activity on the AR signaling axis. Depletion of the MLCP inhibitory subunit PPP1R14C results in sustained MLCP activity towards its substrates. Amongst these, RB1 is maintained in a hypophosphorylated state, which represses E2F1 mediated cell cycle progression and the associated AR phosphorylation events by CDKs. This leads to enhanced AKT mediated proteasomal degradation of the AR culminating in significant repression of AR target gene expression. Phenotypically this reduces cell cycle progression, proliferation and migration. Conversely, depletion of the MLCP substrate specifying subunit PPP1R12A, representative of MLCP inhibition, results in enhanced AR gene and protein expression and subsequent target gene expression.