Polypyrimidine Tract-Binding Protein-Associated Splicing Factor Is a Negative Regulator of Transcriptional Activity of the Porcine P450scc Insulin-Like Growth Factor Response Element

Urban, Randall J.; Bodenburg, Yvonne H.; Kurosky, Alexander; Wood, Thomas G.; Gasic, Slavisa

doi:10.1210/mend.14.6.0485

Cited by 65 publications

(16 citation statements)

References 33 publications

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“…www.pnas.org͞cgi͞doi͞10.1073͞pnas.0508805102 (2,3). We reported that PSF also represses oncogenic genes (OG), and that retroviral-mediated transfection of VL30 retroelement RNA into a human nonmetastatic tumor line formed a PSF-VL30 RNA complex that reversed repression by PSF and promoted metastasis (4,5).…”

mentioning

confidence: 99%

Roles of PSF protein and VL30 RNA in reversible gene regulation

Sun

Garen

2005

Proc. Natl. Acad. Sci. U.S.A.

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The mammalian protein PSF contains a DNA-binding domain (DBD) that coordinately represses multiple oncogenic genes in human cell lines, indicating a role for PSF as a human tumor-suppressor protein. PSF also contains two RNA-binding domains (RBD) that form a complex with a noncoding VL30 retroelement RNA, releasing PSF from a gene and reversing repression. Thus, the DBD and RBD in PSF are linked by a mechanism of reversible gene regulation involving a noncoding RNA. This mechanism also could apply to other regulatory proteins that contain both DBD and RBD. The mouse genome has multiple copies of VL30 retroelements that are developmentally regulated, and mouse cells contain VL30 RNAs that have normal and pathological roles in gene regulation. Human chromosome 11 has a VL30 retroelement, and a VL30 EST was identified in human blastocyst cells, indicating that the PSF-VL30 RNA regulatory mechanism also could function in human cells.

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mentioning

confidence: 99%

Roles of PSF protein and VL30 RNA in reversible gene regulation

Sun

Garen

2005

Proc. Natl. Acad. Sci. U.S.A.

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“…PSF represses the porcine gene P450scc, by binding to the IGFRE motif in the gene (5,6). Our finding that mVL30-1 RNA induces transcription of the homologous human P450scc gene (Table 1) and forms a complex with PSF (Fig.…”

Section: Mapping the Tracts In Mvl30-1 Rna That Form A Complex With Psfmentioning

confidence: 73%

“…The protein was originally identified as a component of spliceosomes (3) and later shown to function as a repressor of the IGF1-inducible gene P450ssc, which controls a rate-limiting step in steroid synthesis (5). Repression of P450scc involves binding of PSF to an IGFRE motif of the gene (5), and the complex formed with mVL30-1 RNA inhibits and dissociates the binding of PSF to the IGFRE (see Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Dependence on mVL30-1 RNA was surprising because the RNA seems to lack significant coding potential. Here, we report that mVL30-1 RNA forms a complex with PSF, a multifunctional regulatory protein that binds to RNA in spliceosomes (3,4) and to an IGFRE motif in the insulin-like growth factor 1 (IGF1)-inducible gene P450ssc that represses transcription of the gene (5,6). The complex with mVL30-1 RNA releases PSF, allowing transcription to proceed.…”

mentioning

confidence: 99%

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Binding of mouse VL30 retrotransposon RNA to PSF protein induces genes repressed by PSF: Effects on steroidogenesis and oncogenesis

Sui

Garen

2004

Proc. Natl. Acad. Sci. U.S.A.

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We describe a mechanism of gene regulation involving formation of a complex between PSF protein and mouse VL30 (mVL30) retrotransposon RNA. PSF represses transcription of the insulin-like growth factor 1 (IGF1)-inducible gene P450scc by binding to an insulin-like growth factor response element (IGFRE) motif in the gene. The complex with mVL30 RNA releases PSF, allowing transcription to proceed. Retrovirally mediated transmission of mVL30 RNA to human tumor cells induced several genes, including oncogenes, which also are induced by IGF1, and promoted metastasis. In mice, steroid synthesis is activated in steroidogenic cells by pituitary hormones, which concomitantly induce transcription of mVL30 RNA in the cells. We showed that steroid synthesis could also be activated in mouse steroidogenic adrenal cells by transfection with cDNA encoding either mVL30 RNA tracts that form a complex with PSF or a small interfering RNA (siRNA) that degrades PSF transcripts. These results suggest that mVL30 RNA regulates steroidogenesis, and possibly other physiological processes of mice, by complex formation with PSF. Retrotransposons such as mVL30 apparently evolved not only as ''junk'' DNA but also as transcriptionally active noncoding DNA that acquired physiological and pathological functions. The complete genome of a mouse VL30 (mVL30) retrotransposon is structurally similar to a retroviral genome, with 5Ј and 3Ј LTRs flanking an internal region containing Ϸ3.7 kb (1). In contrast to the internal region of an infectious retroviral genome that encodes gag, pol, and env proteins, the corresponding region of the mVL30 genome has numerous stop codons in all reading frames that probably block formation of a functional protein. The mouse genome contains multiple copies of transcriptionally active mVL30 DNA, and virtually all mouse cells contain mVL30 RNA although the level varies among different tissues and at different developmental stages (1). Because retroviral vectors for gene transfer and gene therapy usually are produced in packaging cells derived from mouse cells, these cells also contain mVL30 RNA. A remarkable property of retroviral vectors is the capacity to transmit mVL30 RNA from a packaging cell to cells infected by the retrovirus, which synthesize, integrate, and transcribe mVL30 cDNA (1). In an earlier report (2), we showed that retroviral-mediated transfection of tissue factor (TF) cDNA into a nonmetastatic human melanoma cell line increased the metastatic potential of the cells to which mVL30-1 RNA also had been transmitted. The increase in metastatic potential depended on expression of TF protein on the cell surface and also on transcription of mVL30-1 cDNA. Dependence on mVL30-1 RNA was surprising because the RNA seems to lack significant coding potential. Here, we report that mVL30-1 RNA forms a complex with PSF, a multifunctional regulatory protein that binds to RNA in spliceosomes (3, 4) and to an IGFRE motif in the insulin-like growth factor 1 (IGF1)-inducible gene P450ssc that represses transcription of the g...

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“…21 In some cases, higher values may be calculation artifacts due to an uneven gel run, with this effect being relatively greater in the high molecular weight region of gels. In others, they are due to an anomalous migration on SDS-PAGE due to intrinsic characteristics of the molecule, as is the case for PTB-associated splicing factor 22 and moesin. 23 Function analysis (Figure 4) shows that the proteins identified are distributed among the following groups: cytoskeleton/ migration (24.7%), metabolism (17.6%), granule secretory components (11.3%), gene regulation (10.3%), protein synthesis/ modification/degradation (7.2%), membrane fusion/trafficking (6.2%), chaperones and protein folding (5.2%), redox (4.1%), bactericidal mechanisms (4.1%), signaling (3.1%), calciumbinding (3.1%) and receptors (1.0%).…”

Section: Separation Of Proteins From Whole Eosinophil Extracts and Cymentioning

confidence: 99%

The Human Eosinophil Proteome. Changes Induced by Birch Pollen Allergy

et al. 2009

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Proteins from human eosinophils were separated bidimensionally and identified by mass spectrometry (336 spots/bands, 98 different proteins). Of these, 24.7% belonged to the cytoskeleton/migration group. Highly basic proteins (11.3%) were concentrated in the granule-containing cell fraction. We detected novel hyperacidic forms of cofilin-1, profilin-1 and adenylyl cyclase-associated protein, and hyperbasic forms of eosinophil-derived neurotoxin/eosinophil protein X and major basic protein homologue. We also found evidence of the triglycosylation of the heavy chain of eosinophil peroxidase. In addition, through comparative 2D image analysis, spot quantification and MS, it was found that hsc70, actin-capping protein and hyperacidic forms of eosinophil peroxidase heavy chain are overexpressed in cells from birch pollen allergic subjects, at the peak of a season. The link between these findings and an increased cellular antigen-presenting capacity and motility are discussed.

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Polypyrimidine Tract-Binding Protein-Associated Splicing Factor Is a Negative Regulator of Transcriptional Activity of the Porcine P450scc Insulin-Like Growth Factor Response Element

Cited by 65 publications

References 33 publications

Roles of PSF protein and VL30 RNA in reversible gene regulation

Roles of PSF protein and VL30 RNA in reversible gene regulation

Binding of mouse VL30 retrotransposon RNA to PSF protein induces genes repressed by PSF: Effects on steroidogenesis and oncogenesis

The Human Eosinophil Proteome. Changes Induced by Birch Pollen Allergy

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