FIGURE 12.

Interactions between AR, MAGE-11, and TIF2. A, schematic diagram of dynamic interactions between AR (blue), MAGE-11 (orange), and TIF2 (light blue) in the context of the AR antiparallel dimer bound to DNA. Indicated is the AR NH₂-terminal (N) activation function 1 (AF1), AR carboxyl-terminal (C) activation function 2 (AF2), and the AR FXXLF motif interaction site for MAGE-11 and AF2 in the N/C interaction. B, detailed schematic diagram of interactions between MAGE-11 (orange) F-box residues 329–369 in the carboxyl-terminal MAGE homology domain (MHD) with the AR (blue) NH₂-terminal FXXLF motif ²³FQNLF²⁷, which is modulated by phosphorylation in the MAGE-11 F-box at Thr-360, monoubiquitinylation (Ub) at Lys-240 and -245 (19), and serum stimulation of MAP kinase phosphorylation of MAGE-11 Ser-174 outside the F-box. AR transcriptional activity is increased by MAGE-11 F-box binding of the AR FXXLF motif, which competitively inhibits AR FXXLF motif binding to AF2 in the AR N/C interaction. This exposes AF2 in the AR ligand binding domain (LBD) for TIF2 (light blue) LXXLL (LX) motif binding. MAGE-11 also increases AR transcriptional activity through direct interactions with the TIF2 NH₂-terminal region and with AD1 mediated in part by MAGE-11 FXXIF motif ²⁶⁰FPEIF²⁶⁴.