Transcriptional activity of androgen receptor is modulated by two RNA splicing factors, PSF and p54nrb.
Nuclear receptors regulate gene activation or repression through dynamic interactions with coregulators. The interactions between nuclear receptors and RNA splicing factors link gene transcription initiation with pre-mRNA splicing, providing a coordinated control of the products of gene transcription. Here we report that two RNA splicing factors, PTB-associated splicing factor (PSF) and p54nrb, synergistically form protein complexes with the androgen receptor (AR) in a ligand-independent manner and inhibit its transcriptional activity. PSF does not affect AR protein stability, as in the case of the progesterone receptor, but impedes the interaction of AR with the androgen response element. Both splicing factors interact directly with mSin3A and attract mSin3A to the AR complex in a synergistic manner. The suppression of AR transcriptional activity by PSF and p54nrb is reversed by the inhibition of histone deacetylase activity. These data demonstrated that PSF and p54nrb complex with AR and play a key role in modulating AR-mediated gene transcription.
Dong
Xuesen
X
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, 600 University Avenue, Toronto, Canada.
Sweet
Joan
J
Challis
John R G
JR
Brown
Theodore
T
Lye
Stephen J
SJ
D002460:Cell Line; D004268:DNA-Binding Proteins; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D050810:Octamer Transcription Factors / Q000378:metabolism*; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000235:genetics; D011485:Protein Binding; D012326:RNA Splicing / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D011944:Receptors, Androgen / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D015533:Transcriptional Activation
C410798:AR protein, human; D004268:DNA-Binding Proteins; C083214:NONO protein, human; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D016601:RNA-Binding Proteins; D011944:Receptors, Androgen; D012097:Repressor Proteins; C099683:SIN3A transcription factor; D038941:Polypyrimidine Tract-Binding Protein; D017430:Prostate-Specific Antigen; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D056264:Sin3 Histone Deacetylase and Corepressor Complex