p54nrb acts as a transcriptional coactivator for activation function 1 of the human androgen receptor.
The androgen receptor (AR) has two transactivation functions that have been mapped to the N- and C-terminal domains and designated as activation function-1 (AF-1) and AF-2, respectively. While the molecular basis for AF-2 function has been well studied, little is known about AF-1 coregulators. Therefore, we attempted to identify AF-1-interacting proteins from HEK293 cells by biochemical purification followed by mass fingerprinting by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Purified AF-1 region-interacting proteins were found to contain nuclear RNA-binding protein p54(nrb), polypyrimidine tract-binding protein-associated splicing factor (PSF), paraspeckle protein 1 (PSP1), and PSP2, which are assumed to be involved in pre-mRNA processing. p54(nrb) interacted with AR via the A/B domain in a ligand-dependent manner. Reflecting the physical interaction between p54(nrb) and the AR A/B domain, AR AF-1 function was potentiated by p54(nrb). Our results suggest that p54(nrb) functions as a coactivator of AR that potentiates transcription, and presumably splicing as well.
Pubmed ID: 12810069 RIS Download
Cell Line | Genes, Reporter | Humans | Nuclear Matrix-Associated Proteins | Nuclear Proteins | Octamer Transcription Factors | Peptide Mapping | Protein Binding | Protein Structure, Tertiary | RNA-Binding Proteins | Receptors, Androgen | Recombinant Fusion Proteins | Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization | Transcriptional Activation