Article

p54(nrb) acts as a transcriptional coactivator for activation function 1 of the human androgen, receptor

Department of Obstetrics and Gynecology, Keio University, Edo, Tōkyō, Japan
Biochemical and Biophysical Research Communications (Impact Factor: 2.3). 08/2003; 306(3):660-5. DOI: 10.1016/S0006-291X(03)01021-0
Source: PubMed

ABSTRACT

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.

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    • "(Dong et al., 2009). In contrast to the many reported repressive effects, NonO has a transcriptional coactivator function in androgen receptor-mediated transcription (Ishitani et al., 2003; Kuwahara et al., 2006). NonO also activates transcription by enhancing the association of many transcription factors, such as E47, OTF-1 and OTF-2, with their target DNAs (Yang et al., 1997). "
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    • "About twenty years ago the group of Harris Busch purified and characterized a heterodimer consisting of a 52 and a 100 kDa subunit, most certainly corresponding to what is nowadays known as the 54 kDa nuclear RNA-binding protein (p54nrb/NONO) and the polypyrimidine tract-binding protein-associated splicing factor (PSF/SFPQ). NONO and SFPQ show 71% sequence identity and, together with paraspeckle component 1 (PSPC1), belong to a subfamily of RNA recognition motif (RRM) proteins defined by tandem RRM motifs, flanked by an additional region of sequence similarity predicted to promote formation of heteromeric complexes between each of the proteins (24). NONO and SFPQ have been implicated in nuclear retention of A- to I-edited RNA as paraspeckle components (25), pre-mRNA 3′-end formation (26), cAMP cycling (27) and transcriptional activation (28–30). Interestingly, apart from their functions in RNA biogenesis, NONO and SFPQ were reported to interact with DNA in vitro, which lead to an investigation of their function in the context of DNA repair. "
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    • "Recently, it has been reported that p54 nrb regulates the activity of transcription factors such as AR, SOCS3, SOX9, and CREB [15] [16] [17] [18]. "
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