NH<sub>2</sub>terminus of PTB-associated splicing factor binds to the porcine P450scc IGF-I response element

Urban, Randall J.; Bodenburg, Yvonne H.; Wood, Thomas G.

doi:10.1152/ajpendo.00057.2002

Cited by 25 publications

(23 citation statements)

References 29 publications

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“…4 To confirm this, we used a biotinylated oligoribonucleotide containing the AREs of the TNF␣ mRNA and, as negative control, one lacking AREs. PSF and p54 nrb were retained on the AREcontaining oligoribonucleotide but not the negative control (Fig.…”

Section: Resultsmentioning

confidence: 99%

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The PSF·p54nrb Complex Is a Novel Mnk Substrate That Binds the mRNA for Tumor Necrosis Factor α

Buxadé

Morrice

Krebs

et al. 2008

Journal of Biological Chemistry

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To identify new potential substrates for the MAP kinase signal-integrating kinases (Mnks), we employed a proteomic approach. The Mnks are targeted to the translational machinery through their interaction with the cap-binding initiation factor complex. We tested whether proteins retained on cap resin were substrates for the Mnks in vitro, and identified one such protein as PSF (the PTB (polypyrimidine tract-binding protein)-associated splicing factor). Mnks phosphorylate PSF at two sites in vitro, and our data show that PSF is an Mnk substrate in vivo. We also demonstrate that PSF, together with its partner, p54 nrb , binds RNAs that contain AU-rich elements (AREs), such as those for proinflammatory cytokines (e.g. tumor necrosis factor ␣ (TNF␣)). Indeed, PSF associates specifically with the TNF␣ mRNA in living cells. PSF is phosphorylated at two sites by the Mnks. Our data show that Mnk-mediated phosphorylation increases the binding of PSF to the TNF␣ mRNA in living cells. These findings identify a novel Mnk substrate. They also suggest that the Mnk-catalyzed phosphorylation of PSF may regulate the fate of specific mRNAs by modulating their binding to PSF⅐p54 nrb .Polypyrimidine tract-binding protein (PTB) 3 -associated splicing factor (PSF) and p54 nrb are highly homologous DNA/ RNA-binding proteins that form a multifunctional heterodimer implicated in nuclear processes such as transcription, nuclear RNA processing, nuclear retention of edited RNA, DNA relaxation, and tumorigenesis (reviewed in Ref. 1). These proteins also cooperate in the inhibition of human immunodeficiency virus type 1 mRNA expression (2). Moreover, PSF is also been reported to repress gene expression through its association with nuclear hormone receptors (3) or through binding to insulin-like growth factor-1 response elements (4). PSF and p54 nrb are both phosphoproteins. Phosphorylation may be involved in the relocalization of PSF during apoptosis (5) and in regulating the binding properties of p54 nrb during mitosis (6). All eukaryotic cytoplasmic mRNAs have a 5Ј-terminal cap structure that contains 7-methyl-GTP (m 7 GTP) and promotes their efficient translation (7,8). The cap is bound by eukaryotic translation initiation factor eIF4E, which also binds to the scaffold eIF4G and through this with other translational factors to recruit the 40 S ribosomal subunit to the mRNA. eIF4G also binds the poly(A)-binding protein (PABP), which interacts with the 3Ј-end of the mRNA, thus circularizing it (reviewed in Ref. 9). eIF4E is phosphorylated in vitro and in vivo by the MAP kinase-signal integrating (or MAP kinase-interacting) kinases (Mnks) (10 -13). There are two Mnk genes in humans, each of which generates two different polypeptides as a consequence of alternative splicing (14, 15). The longer Mnk1 isoform, Mnk1a, is switched on by signaling through the ERK and p38 MAP kinase pathways, whereas Mnk2a (the longer Mnk2 isoform), in contrast, shows high basal activity (11,16,17). We recently showed that Mnks play an important role in the control ...

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Section: Resultsmentioning

confidence: 99%

“…These proteins also cooperate in the inhibition of human immunodeficiency virus type 1 mRNA expression (2). Moreover, PSF is also been reported to repress gene expression through its association with nuclear hormone receptors (3) or through binding to insulin-like growth factor-1 response elements (4). PSF and p54 nrb are both phosphoproteins.…”

mentioning

confidence: 99%

The PSF·p54nrb Complex Is a Novel Mnk Substrate That Binds the mRNA for Tumor Necrosis Factor α

Buxadé

Morrice

Krebs

et al. 2008

Journal of Biological Chemistry

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“…The protein associates with PTB to form spliceosomes for splicing of pre-mRNA. The amino terminus is rich in proline and glutamine residues and was shown in a previous study to contain the amino acid residues that bind the porcine P450scc IGFRE (13).…”

Section: Insulin-like Growth Factor I (Igf-imentioning

confidence: 97%

PTB-associated splicing factor regulates growth factor-stimulated gene expression in mammalian cells

Urban

Bodenburg

2002

American Journal of Physiology-Endocrinology and Metabolism

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An insulin-like growth factor I (IGF-I) response element (IGFRE) in the porcine P-450 cholesterol side-chain cleavage gene (P450scc) binds two transcription factors, Sp1 and polypyrimidine tract-binding protein-associated splicing factor (PSF). In this study, we investigated expression of these transcription factors in mouse Y1 adrenal cells, a cell line that does not increase P450scc expression in response to IGF-I. Western blot analysis showed a greater expression of PSF in Y1 cells when compared with a mouse fibroblast cell line (NWTb3) in which IGF-I stimulates the P450scc IGFRE. The two cell lines expressed Sp1 equally, and IGF-I did not increase expression of either transcription factor. Chromatin immunoprecipitation analysis with Y1 chromatin confirmed that PSF and Sp1 bound to the IGFRE. When increasing amounts of Sp1 were expressed in Y1 cells, the IGFRE became responsive to IGF-I. Moreover, a mutant oligonucleotide IGFRE reporter construct that lacks PSF binding was responsive to IGF-I. In conclusion, Y1 adrenal cells are a physiological example of PSF repression of growth factor-stimulated (IGF-I) gene expression (P450scc). The dynamic nature of this repression is consistent with PSF functioning as a regulator of growth factor-stimulated gene expression in mammalian cells.

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“…One of its primary roles is as a component of spliceosomes and it is mediated by its RNA-binding domains (RBD) (7). In addition, PSF has been identified as a transcriptional regulator of the gene encoding for P450-linked side chain cleaving enzyme, which initiates the steroidogenic pathway, and binds to its regulatory region through its DNA-binding domain (DBD) (8,9). The RBD and DBD function independently and their novel mechanisms for reversible gene transcription mediated by PSF protein and noncoding RNA have been investigated.…”

Section: Introductionmentioning

confidence: 99%

Binding of LINE-1 RNA to PSF transcriptionally promotes GAGE6 and regulates cell proliferation and tumor formation in vitro

Zhao

2017

Experimental and Therapeutic Medicine

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Abstract. Hepatocellular carcinoma (HCC) has one of the highest mortality rates among numerous types of cancer. It has been demonstrated that in hepatitis B (HBV)-associated HCC, the expression of chimeric fusion transcript HBx-long interspersed nuclear element-1 (LINE-1) initiated by HBV integration is correlated with hepatocarcinogenesis and poor patient survival rates. Furthermore, increased rates of LINE-1 hypomethylation have been detected in HCC tissues compared with adjacent tissues. This suggests that individual LINE-1 RNA (L1 RNA) serves an important role in the processes of hepatocarcinogenesis. The present study assessed the epigenic interaction between L1 RNA and polypyrimidine tract-binding protein-associated splicing factor (PSF) in the A549 human alveolar epithelial and 16HBE human bronchial epithelial cell lines. In addition, changes in the transcriptional regulatory activity of PSF on its target gene, proto-oncogene G antigen 6 (GAGE6), were investigated following overexpression of L1 RNA, as well as its impact on cell-proliferative capacity, carried out by plotting cell growth curves and 5-ethynyl-2'-deoxyuridine assay. It was observed that L1 RNA specifically bound to the RNA binding domain of PSF and released the GAGE6 promoter region from the DNA-binding domain of PSF. This increased the transcription of GAGE6 and led to the promotion of cell proliferation as well as colony formation. Furthermore, at least two binding sites specific for PSF were identified on L1 RNA. In conclusion, the transcriptional regulatory activity of L1 RNA may partially result in cell transformation, and endogenous L1 RNA may function as an important regulatory factor in the process of tumorigenesis.

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NH₂terminus of PTB-associated splicing factor binds to the porcine P450scc IGF-I response element

Cited by 25 publications

References 29 publications

The PSF·p54nrb Complex Is a Novel Mnk Substrate That Binds the mRNA for Tumor Necrosis Factor α

The PSF·p54nrb Complex Is a Novel Mnk Substrate That Binds the mRNA for Tumor Necrosis Factor α

PTB-associated splicing factor regulates growth factor-stimulated gene expression in mammalian cells

Binding of LINE-1 RNA to PSF transcriptionally promotes GAGE6 and regulates cell proliferation and tumor formation in vitro

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NH2terminus of PTB-associated splicing factor binds to the porcine P450scc IGF-I response element

Cited by 25 publications

References 29 publications

The PSF·p54nrb Complex Is a Novel Mnk Substrate That Binds the mRNA for Tumor Necrosis Factor α

The PSF·p54nrb Complex Is a Novel Mnk Substrate That Binds the mRNA for Tumor Necrosis Factor α

PTB-associated splicing factor regulates growth factor-stimulated gene expression in mammalian cells

Binding of LINE-1 RNA to PSF transcriptionally promotes GAGE6 and regulates cell proliferation and tumor formation in vitro

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NH₂terminus of PTB-associated splicing factor binds to the porcine P450scc IGF-I response element