Identification of SP3 as a Negative Regulatory Transcription Factor in the Monocyte Expression of Growth Hormone

Vines, Clifford R.

doi:10.1210/en.141.3.938

Cited by 7 publications

(3 citation statements)

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“…It should also be noted that SP-1 binding may also increase after stress and confer resistance to oxidative stress [49]. In a previous report, we showed that SP transcription factors bind to the region at −138/−133 bp containing a GGGAGG motif in the GH promoter and appeared to inhibit GH promoter luciferase activity in the P-388 monocyte cell line [50]. Although this result may initially appear puzzling, the two studies were done in different cell lines and under different experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

High molecular weight isoforms of growth hormone in cells of the immune system

Weigent

2011

Cellular Immunology

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A substantial body of research exists to support the idea that cells of the immune system produce growth hormone (GH). However, the structure and mechanism of action of lymphocyte-derived GH continues to remain largely unknown. Here we present the results of Western analysis of whole cell extracts showing that different molecular weight isoforms of GH of approximately 100 kDa, 65 kDa, and 48 kDa can be detected in primary mouse cells of the immune system and in the mouse EL4 cell line. The identity of the 65 kDa and 48 kDa isoforms of GH were confirmed by mass spectrometry. The various isoforms were detected in both enriched T and B spleen cell populations. The large molecular weight isoform appears to reside primarily in the cytoplasm whereas the lower molecular weight 65 kDa and 48 kDa isoforms were detected primarily in the nucleus. These results also suggest that GH isoforms are induced by oxidative stress. In EL4 cells overexpressing GH, the expression of luciferase controlled by a promoter containing the antioxidant response element is increased almost three-fold above control. The data suggest that the induction of isoforms of the GH molecule in cells of the immune system may be an important mechanism of adaptation and/or protection of lymphoid cells under conditions of oxidative stress.

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Section: Discussionmentioning

confidence: 99%

High molecular weight isoforms of growth hormone in cells of the immune system

Weigent

2011

Cellular Immunology

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“…Therefore, it is reasonable to expect they also compete for binding to promoters containing GC-boxes. In fact, these two factors have been shown to display differential activity, including parallel or opposing transcription effects depending on the promoter (Conn et al 1996, Kennett et al 1997, Hata et al 1998, Hoppe & Francone 1998, Nielsen et al 1998, Rajakumar et al 1998, Yajima et al 1998, Merchant et al 1999, Vines & Weigent 2000. Cell-type-specific levels of Sp1 and Sp3 variants have the potential to be an important mode of regulating the contribution of Sp1 to promoter activity.…”

Section: Role Of Sp1 In Basal Transcriptionmentioning

confidence: 99%

Role of Sp1 in insulin regulation of gene expression

Samson

Wong²

2002

Journal of Molecular Endocrinology

142

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Sp1 is a ubiquitous nuclear factor that plays a key role in maintaining basal transcription of 'house-keeping' genes. However, recent evidence points to a more important function for Sp1 in mediating 'cross-talk' between selected signaling cascades to regulate the target genes that respond to these pathways. The role of Sp1 in mediating the actions of the peptide hormone insulin is of specific interest and serves as a model for detailing effects of intracellular signaling on Sp1 activity. This review summarizes studies suggesting that changes in Sp1 phosphorylation provide one potential mechanism for manipulating activity of this protein. A growing body of evidence reveals that the DNA binding and transcription activity of Sp1 may increase or decrease in response to changes in phosphorylation. This enables 'fine-tuning' of Sp1 activity for regulation of gene transcription. Several mechanisms exist by which Sp1 alters gene activity in response to insulin. These include independent Sp1 activity as well as collaboration or competition with others factors. This review points to an ever-increasing role for Sp1 in regulating the transcription of genes in response to extracellular signals such as insulin.

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“…Sp1 and Sp3 compete for binding to GC-boxes and display differential activity, including parallel or opposing transcription effects depending on the promoter [46]–[54] or cell type [29]. That Sp1 and Sp3 bind to hres regulatory sequences was further confirmed by site directed mutagenesis of Sp1 binding site and ChIP assay.…”

Section: Discussionmentioning

confidence: 83%

Transcription of Human Resistin Gene Involves an Interaction of Sp1 with Peroxisome Proliferator-Activating Receptor Gamma (PPARγ)

et al. 2010

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BackgroundResistin is a cysteine rich protein, mainly expressed and secreted by circulating human mononuclear cells. While several factors responsible for transcription of mouse resistin gene have been identified, not much is known about the factors responsible for the differential expression of human resistin.Methodology/Principal FindingWe show that the minimal promoter of human resistin lies within ∼80 bp sequence upstream of the transcriptional start site (−240) whereas binding sites for cRel, CCAAT enhancer binding protein α (C/EBP-α), activating transcription factor 2 (ATF-2) and activator protein 1 (AP-1) transcription factors, important for induced expression, are present within sequences up to −619. Specificity Protein 1(Sp1) binding site (−276 to −295) is also present and an interaction of Sp1 with peroxisome proliferator activating receptor gamma (PPARγ) is necessary for constitutive expression in U937 cells. Indeed co-immunoprecipitation assay demonstrated a direct physical interaction of Sp1 with PPARγ in whole cell extracts of U937 cells. Phorbol myristate acetate (PMA) upregulated the expression of resistin mRNA in U937 cells by increasing the recruitment of Sp1, ATF-2 and PPARγ on the resistin gene promoter. Furthermore, PMA stimulation of U937 cells resulted in the disruption of Sp1 and PPARγ interaction. Chromatin immunoprecipitation (ChIP) assay confirmed the recruitment of transcription factors phospho ATF-2, Sp1, Sp3, PPARγ, chromatin modifier histone deacetylase 1 (HDAC1) and the acetylated form of histone H3 but not cRel, C/EBP-α and phospho c-Jun during resistin gene transcription.ConclusionOur findings suggest a complex interplay of Sp1 and PPARγ along with other transcription factors that drives the expression of resistin in human monocytic U937 cells.

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Identification of SP3 as a Negative Regulatory Transcription Factor in the Monocyte Expression of Growth Hormone

Cited by 7 publications

References 0 publications

High molecular weight isoforms of growth hormone in cells of the immune system

High molecular weight isoforms of growth hormone in cells of the immune system

Role of Sp1 in insulin regulation of gene expression

Transcription of Human Resistin Gene Involves an Interaction of Sp1 with Peroxisome Proliferator-Activating Receptor Gamma (PPARγ)

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