Transcriptional synergy between melanoma antigen gene protein-A11 (MAGE-11) and p300 in androgen receptor signaling.
Androgen receptor (AR)-mediated gene regulation involves interactions with coregulatory proteins that include the melanoma antigen gene protein-A11 (MAGE-11). To understand the functional significance of sequence similarity between MAGE-11 and the adenovirus early protein E1A, we determined whether MAGE-11 contributes to AR transcriptional activity through an interaction with p300, a potent and ubiquitous transcriptional regulator. Here, we report that MAGE-11 interacts with the NH(2)-terminal region of p300 through the MAGE-11 MXXIF motif (185)MXXIF(189), with transcriptional activity depending on the MAGE-11 F-box and MAPK phosphorylation. The MAGE-11- and p300-dependent increase in AR transactivation required the NH(2)-terminal regions of AR and p300, p300 acetyltransferase activity, and the AR FXXLF motif (23)FQNLF(27) interaction with MAGE-11. MAGE-11 linked AR to p300 and the p160 coactivator, transcriptional intermediary protein 2 (TIF2). The p300 NH(2)-terminal FXXLF motif (33)FGSLF(37) was required for transcriptional activation by TIF2. Increased expression of p300 decreased the ubiquitinylation of MAGE-11 and transiently increased endogenous MAGE-11 levels. Autoacetylation of p300 and decreased acetylation of TIF2 were evident in the MAGE-11, p300, and TIF2 complex. The studies suggest that MAGE-11 links NH(2)-terminal domains of AR and p300 to promote transcriptional synergy through a cadre of FXXLF-related interacting motifs.
Askew
Emily B
EB
Department of Pediatrics, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Bai
Suxia
S
Blackwelder
Amanda J
AJ
Wilson
Elizabeth M
EM
D020816:Amino Acid Motifs; D000728:Androgens / Q000378:metabolism; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011944:Receptors, Androgen / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011987:Receptors, Steroid / Q000378:metabolism; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
D000728:Androgens; D000951:Antigens, Neoplasm; C110882:MAGEA11 protein, human; D009363:Neoplasm Proteins; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human
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