p54nrb acts as a transcriptional coactivator for activation function 1 of the human androgen receptor

Ishitani, Ken; Yoshida, Tasuku; Kitagawa, Hirochika; Ohta, Hiroaki; Nozawa, Shiro; Kato, Shigeaki

doi:10.1016/s0006-291x(03)01021-0

Cited by 65 publications

(45 citation statements)

References 27 publications

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“…Thus, p54 nrb had been found to interact with and to coactivate the androgen receptor AF1 domain within a complex including PSF, PSP1 (paraspeckle protein-1), and PSP2, which modulate pre-mRNA processing (32). In addition, PGC-1, which was originally identified as a transcriptional coactivator of the nuclear receptor peroxisome proliferator-activated receptor-␥ and of several nuclear receptors (33,34), has been shown to interact with components of the splicing machinery, therefore allowing coordi- [6][7][8][9][10][11] and increasing amounts of bacterially expressed GST (lanes 6-8) or GST-PSF (lanes 9-11).…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of the Protein-associated Splicing Factor as a Negative Co-regulator of the Progesterone Receptor

Dong

Shylnova

Challis

et al. 2005

Journal of Biological Chemistry

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Progesterone is essential in all species for the maintenance of pregnancy, and its withdrawal is required to activate the myometrium and to initiate labor. However, unlike most other species, progesterone levels do not fall at term in humans, raising the paradox as to how labor can occur under the continued influence of progesterone. We hypothesized that an endogenous (myometrial) repressor of the progesterone receptor (PR) could induce a functional withdrawal of progesterone and hence lead to the initiation of labor. We used the human PR as bait in a protein pull-down assay and identified polypyrimidine tract-binding protein-associated splicing factor (PSF) as a PR-interacting protein. PSF functions as a potent inhibitor of PR (but not estrogen receptor) transcriptional activity in mammalian cells. It acts through two novel mechanisms, inducing degradation of the PR through the proteasomal pathway and also interfering with binding of PR to its DNA response element. Importantly, in vivo studies in rats demonstrated a dramatic increase in myometrial PSF expression at term that was temporally associated with reduced levels of the myometrial PR. Accordingly, we propose that PSF acts as a PR corepressor and contributes to the functional withdrawal of progesterone and the initiation of human labor.Progesterone is an essential regulator of the reproductive events associated with the establishment and maintenance of pregnancy through its ligand-activated progesterone receptor (PR) 1 (1). Progesterone actions include the suppression of genes encoding contraction-associated proteins (e.g. oxytocin and prostaglandin receptors and connexin-43) that are required for myometrial activation and the onset of labor. In humans, progesterone levels remain elevated throughout labor, raising a paradox as to how labor can be initiated. Even in species in which progesterone levels fall at term, concentrations are likely sufficiently high to inhibit contraction-associated protein gene expression. This suggests there must be an active mechanism for inducing a functional withdrawal of progesterone at term. We have previously suggested that a blockade of PR signaling in the myometrium could induce a "functional withdrawal" of progesterone that would result in the initiation of labor (2). A number of mechanisms have been proposed to effect such a functional withdrawal, including changes in the expression of the PR or PR isoforms (3) as well as altered transcriptional activity of the PR as a result of changes in the expression of essential co-regulators (both coactivators and corepressors) (4).The PR is a member of the steroid receptor superfamily of ligand-dependent transcriptional factors. In the human myometrium, the PR is transcribed as full-length PRB and an N-terminally truncated (164 amino acids) PRA isoform (5). PRA is generally a weaker transcriptional activator than PRB (6 -8) and can also act as a repressor of PRB as well as of other steroid receptors (9, 10). Upon ligand binding through the hormone-binding domain, the activated ...

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Section: Discussionmentioning

confidence: 99%

Identification and Characterization of the Protein-associated Splicing Factor as a Negative Co-regulator of the Progesterone Receptor

Dong

Shylnova

Challis

et al. 2005

Journal of Biological Chemistry

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“…GST pull-down assays were performed using GST-Acinus-SЈ C terminus and in vitro-transcribed and -translated [ VOL. 28,2008 Acinus-SЈ IS A MODULATOR OF RAR ACTIVITY 2555 components of basal transcriptional machinery and general coactivators and corepressors, N-terminal A/B domains can interact with proteins involved in processes such as mRNA processing and splicing (p68, SRA, ANT-1, and p54nrb), with chaperones (BAG-1) or with a number of proteins containing specific enzymatic activities such as acetyl-and methyltransferases (12,17,25,34,39,43).…”

Section: Discussionmentioning

confidence: 99%

Acinus-S′ Represses Retinoic Acid Receptor (RAR)-Regulated Gene Expression through Interaction with the B Domains of RARs

Vucetic

Zhu²,

Zhao³

et al. 2008

Molecular and Cellular Biology

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The diverse biological actions of retinoic acid (RA) are mediated by RA receptors (RARs) and retinoid X receptors (RXRs). Modulation of transcription by RARs/RXRs is achieved through two activation functions, ligand-independent AF-1 and ligand-dependent AF-2, located in the A/B and E domains, respectively. While the coregulatory proteins that interact with the E domain are well studied, the A/B domain-interacting partners and their influence(s) on the function of RARs are poorly understood. Acinus-S is an ubiquitous nuclear protein that has been implicated in inducing apoptotic chromatin condensation and regulating mRNA processing. Our data demonstrate that Acinus-S can specifically repress ligand-independent and ligand-dependent expression of a DR5 RA response element(RARE)-dependent reporter gene and several endogenous RAR-regulated genes in a dose-dependent and gene-specific manner. Chromatin immunoprecipitation assays show that Acinus-S associates with RAREs within the promoters of endogenous genes independent of RA treatment. Furthermore, the C-terminal end of Acinus-S and the B domain of RAR␤ interact independently of ligand, and the C-terminal end of Acinus-S is sufficient for the repression of RAR-regulated gene expression. Finally, histone deacetylase activity only partially accounts for the repressive effect of Acinus-S on RAR-dependent gene expression. These findings identify Acinus-S as a novel RAR-interacting protein that regulates the expression of a subset of RAR-regulated genes through direct binding to the N-terminal B domains of RARs.

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“…Similarly a PER complex that rhythmically associates with DNA bound CLOCK-BMAL1 at the Per1 promoter represses transcription by virtue of its constituent SFPQ which recruits the SIN3-HDAC complex to deacetylate histones 3 and 4 (Duong et al 2011). Conversely, in the case of androgen receptor responsive genes, transcriptional activation by SFPQ/ NONO has been demonstrated (Ishitani et al 2003;Kuwahara et al 2006). Further examples of the functional diversity of SFPQ and NONO are their involvement in developmentally linked gene regulation, specifically, in relation to neuronal tissue development (Chanas-Sacré et al 1999;Ju et al 2004) and cell cycle control (Stier et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA

Snijders

Hautbergue

Bloom

et al. 2015

RNA

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Splicing factor proline-and glutamine-rich (SFPQ) also commonly known as polypyrimidine tract-binding protein-associatedsplicing factor (PSF) and its binding partner non-POU domain-containing octamer-binding protein (NONO/p54nrb), are highly abundant, multifunctional nuclear proteins. However, the exact role of this complex is yet to be determined. Following purification of the endogeneous SFPQ/NONO complex, mass spectrometry analysis identified a wide range of interacting proteins, including those involved in RNA processing, RNA splicing, and transcriptional regulation, consistent with a multifunctional role for SFPQ/NONO. In addition, we have identified several sites of arginine methylation in SFPQ/PSF using mass spectrometry and found that several arginines in the N-terminal domain of SFPQ/PSF are asymmetrically dimethylated. Furthermore, we find that the protein arginine N-methyltransferase, PRMT1, catalyzes this methylation in vitro and that this is antagonized by citrullination of SFPQ. Arginine methylation and citrullination of SFPQ/PSF does not affect complex formation with NONO. However, arginine methylation was shown to increase the association with mRNA in mRNP complexes in mammalian cells. Finally we show that the biochemical properties of the endogenous complex from cell lysates are significantly influenced by the ionic strength during purification. At low ionic strength, the SFPQ/NONO complex forms large heterogeneous protein assemblies or aggregates, preventing the purification of the SFPQ/NONO complex. The ability of the SFPQ/NONO complex to form varying protein assemblies, in conjunction with the effect of post-translational modifications of SFPQ modulating mRNA binding, suggests key roles affecting mRNP dynamics within the cell.

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p54nrb acts as a transcriptional coactivator for activation function 1 of the human androgen receptor

Cited by 65 publications

References 27 publications

Identification and Characterization of the Protein-associated Splicing Factor as a Negative Co-regulator of the Progesterone Receptor

Identification and Characterization of the Protein-associated Splicing Factor as a Negative Co-regulator of the Progesterone Receptor

Acinus-S′ Represses Retinoic Acid Receptor (RAR)-Regulated Gene Expression through Interaction with the B Domains of RARs

Arginine methylation and citrullination of splicing factor proline- and glutamine-rich (SFPQ/PSF) regulates its association with mRNA

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