Melanoma antigen-A11 (MAGE-A11) Enhances Transcriptional Activity by Linking Androgen Receptor Dimers

摘要: Prostate cancer growth and progression depend on androgen receptor (AR) signaling through transcriptional mechanisms that require interactions with coregulatory proteins, one of which is the primate-specific steroid coregulator melanoma antigen-A11 (MAGE-A11). In this report, we provide evidence how increased expression MAGE-A11 during prostate enhances AR growth. protein levels were highest in castration-recurrent cancer. The cyclic AMP-induced increase androgen-dependent androgen-independent activity correlated an was inhibited by silencing expression. mediated synergistic LAPC-4 cells. ability to rescue complementary inactive mutants promote coimmunoprecipitation between unlike forms suggests links transcriptionally active dimers. A model for AR·MAGE-A11 multidimeric complex proposed FXXLF motif dimer engages NH2- carboxyl-terminal interaction, whereas second region interacts dimeric MAGE-A11. accounts dual functions interaction binding synergy reported splice variants full-length AR. We conclude cancer, enhanced AMP signaling, increases AR-dependent forming a molecular bridge Background: Melanoma (MAGE-A11) coregulator. Results: mediates stimulatory effects can mutants. Conclusion: linking Significance: new target treatment.