Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 25, Issue 4, Pages 1238-1257Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.25.4.1238-1257.2005
Keywords
-
Categories
Funding
- FIC NIH HHS [R03TW001234] Funding Source: Medline
- NICHD NIH HHS [R01 HD016910, U54 HD035041, HD16910, U54-HD35041, R37 HD016910] Funding Source: Medline
Ask authors/readers for more resources
Gene activation by steroid hormone receptors involves the recruitment of the steroid receptor coactivator (SRC)/p160 coactivator LXXLL motifs to activation function 2 (AF2) in the ligand binding domain. For the androgen receptor (AR), AF2 also serves as the interaction site for the AR NH2-terminal FXXLF motif in the androgen-dependent NH2-terminal and carboxyl-terminal (N/C) interaction. The relative importance of the AR AF2 site has been unclear, since the AR FXXLF motif interferes with coactivator recruitment by competitive inhibition of LXXLL motif binding. In this report, we identified the X chromosome-linked melanoma antigen gene product MAGE-11 as an AR coregulator that specifically binds the AR NH2-terminal FXXLF motif. Binding of MAGE-11 to the AR FXXLF a-helical region stabilizes the ligand-free AR and, in the presence of an agonist, increases exposure of AF2 to the recruitment and activation by the SRC/p160 coactivators. Intracellular association between AR and MAGE-11 is supported by their coimmunoprecipitation and colocalization in the absence and presence of hormone and by competitive inhibition of the N/C interaction. AR transactivation increases in response to MAGE-11 and the SRC/p160 coactivators through mechanisms that include but are not limited to the AF2 site. MAGE-11 is expressed in androgen-dependent tissues and in prostate cancer cell lines. The results suggest MAGE-11 is a unique AR coregulator that increases AR activity by modulating the AR interdomain interaction.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available