MAGEA11 - Androgen Receptor

Androgen Receptor

MAGE-A11 is part of the androgen receptor signaling pathway in humans. It binds directly to the androgen receptor, promoting transcriptional through direct binding to the androgen receptor FXXLF motif region. This control is specific to primates, and is due to a mutation in the androgen receptor from alanine to valine at residue 33, which extends the α-helix, which enables direct MAGE-A11 binding to the androgen receptor. Post-translational modification of the protein by phosphorylation of Thr-360 and monoubiquitinylation of Lys-240 and Lys-245 also stabilizes the interaction with the androgen receptor. MAGE-A11 likely links transcriptionally active androgen receptor dimers. The MAGE-A11 dependent increase in androgen receptor transcriptional activity is mediated by a direct interaction of MAGE-A11 and transcriptional intermediary factor 2 (TIF2), suggesting that MAGE-A11 may act as a bridging factor to recruit other androgen receptor coactivators. Mutations in the androgen receptor that interfere with binding of MAGE-A11 can cause partial androgen insensitivity syndrome.