Melanoma antigen gene protein-A11 (MAGE-11) F-box links the androgen receptor NH2-terminal transactivation domain to p160 coactivators.

Androgen-dependent transcriptional activity by the androgen receptor (AR) and its coregulators is required for male reproductive development and function. In humans and other primates, melanoma antigen gene protein-A11 (MAGE-11) is an AR selective coregulator that increases AR transcriptional activity. Here we show that the interaction between AR and MAGE-11 is ...
mediated by AR NH(2)-terminal FXXLF motif binding to a highly conserved MAGE-11 F-box in the MAGE homology domain, and is modulated by serum stimulation of mitogen-activated protein kinase phosphorylation of MAGE-11 Ser-174. The MAGE-11-dependent increase in AR transcriptional activity is mediated by a direct interaction between MAGE-11 and transcriptional intermediary factor 2 (TIF2) through the NH(2)-terminal region of TIF2, and by a MAGE-11 FXXIF motif interaction with an F-box-like region in activation domain 1 of TIF2. The results suggest that MAGE-11 functions as a bridging factor to recruit AR coactivators through a novel FXX(L/I)F motif-F-box interaction paradigm.
Mesh Terms:
Amino Acid Sequence, Animals, Antigens, Neoplasm, COS Cells, Cercopithecus aethiops, F-Box Motifs, Humans, Male, Mitogen-Activated Protein Kinases, Molecular Sequence Data, Neoplasm Proteins, Nuclear Receptor Coactivator 2, Prostatic Neoplasms, RNA, Small Interfering, Receptors, Androgen, Sequence Alignment, Transcriptional Activation
J. Biol. Chem.
Date: Dec. 11, 2009
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