A Kinase/Phosphatase System Involving the Protooncogene Lck Is Necessary for Inducible Modulation of Sob 1 during T Cell Activation

Benson, Beverly; Butler, Yun X.; Ackermann, Matt; Benedict, Stephen H.

doi:10.1006/cimm.1996.0158

Cited by 3 publications

(3 citation statements)

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“…Nuclear extracts from growing MSC‐HIF‐1α cells were prepared according to the method of Dignam et al [28]. Nuclear extracts were analyzed by gel shift assays as described previously [29]. Thirty micrograms of nuclear extract was added to 0.8 ng of the labeled double‐stranded oligonucleotide, and, after a 20‐minute incubation at room temperature, the mixture was run on a 6% acrylamide, nondenaturing gel in 0.5 × Tris/Borate/EDTA at 150 V for 90 minutes.…”

Section: Methodsmentioning

confidence: 99%

Evidence for Transcriptional Regulation of the Glucose-6-Phosphate Transporter by HIF-1α: Targeting G6PT with Mumbaistatin Analogs in Hypoxic Mesenchymal Stromal Cells

et al. 2009

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Mesenchymal stromal cell (MSC) markers are expressed on brain tumor-initiating cells involved in the development of hypoxic glioblastoma. Given that MSCs can survive hypoxia and that the glucose-6-phosphate transporter (G6PT) provides metabolic control that contributes to MSC mobilization and survival, we investigated the effects of low oxygen (1.2% O 2 ) exposure on G6PT gene expression. We found that MSCs significantly expressed G6PT and the glucose-6-phosphatase catalytic subunit b, whereas expression of the glucose-6-phosphatase catalytic subunit a and the islet-specific glucose-6-phosphatase catalytic subunit-related protein was low to undetectable. Analysis of the G6PT promoter sequence revealed potential binding sites for hypoxia inducible factor (HIF)-1a and for the aryl hydrocarbon receptor (AhR) and its dimerization partner, the AhR nuclear translocator (ARNT), AhR:ARNT. In agreement with this, hypoxia and the hypoxia mimetic cobalt chloride induced the expression of G6PT, vascular endothelial growth factor (VEGF), and HIF-1a. Gene silencing of HIF-1a prevented G6PT and VEGF induction in hypoxic MSCs whereas generation of cells stably expressing HIF-1a resulted in increased endogenous G6PT gene expression. A semisynthetic analog of the polyketide mumbaistatin, a potent G6PT inhibitor, specifically reduced MSC-HIF-1a cell survival. Collectively, our data suggest that G6PT may account for the metabolic flexibility that enables MSCs to survive under conditions characterized by hypoxia and could be specifically targeted within developing tumors.

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Section: Methodsmentioning

confidence: 99%

Evidence for Transcriptional Regulation of the Glucose-6-Phosphate Transporter by HIF-1α: Targeting G6PT with Mumbaistatin Analogs in Hypoxic Mesenchymal Stromal Cells

et al. 2009

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“…Nuclear extracts from growing or from 4-day serum-starved NIH/3T3 fibroblasts were prepared according to the method of Dignam et al (47). Nuclear extracts were analyzed by gel shift assays as described previously (48). 5 g of nuclear extract were added to 0.8 ng of the labeled doublestranded oligonucleotide, and, after a 20-min incubation at room temperature, the mixture was run on a 6% acrylamide, non-denaturing gel in 0.5ϫ TBE, at 150 V for 90 min.…”

Section: And 2)mentioning

confidence: 99%

“…The identity of band D is not known, and it is reported as being nonspecific in some studies (80). Band B is believed to be a dimer of SRF (48), and band A consists of the SRF homodimer and an unknown factor (80), most likely a TCF member. A strong collaboration between ETS proteins and the SRF has already been proposed (81), and it is interesting to note that an Ets binding site (EBS) is present at position Ϫ489, between the SRE1 and SRE2 (Fig.…”

Section: Mapping Of the Functional Elements Associated With The Growtmentioning

confidence: 99%

Modulation of Apolipoprotein D and Apolipoprotein E mRNA Expression by Growth Arrest and Identification of Key Elements in the Promoter

Carmo

Séguin

Milne

et al. 2002

Journal of Biological Chemistry

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Apolipoprotein D (apoD) and apolipoprotein E (apoE) are co-expressed in many tissues, and, in certain neuropathological situations, their expression appears to be under coordinate regulation. We have previously shown that apoD gene expression in cultured human fibroblasts is up-regulated when the cells undergo growth arrest. Here, we demonstrate that, starting around day 2 of growth arrest, both apoD and apoE mRNA levels increase between 1.5-and 27-fold in other cell types, including mouse primary fibroblasts and fibroblast-like and human astrocytoma cell lines. To understand the regulatory mechanisms of apoD expression, we have used apoD promoter-luciferase reporter constructs to compare gene expression in growing cells and in cells that have undergone growth arrest. Analysis of gene expression in cells transfected with constructs with deletions and mutations in the apoD promoter and constructs with artificial promoters demonstrated that the region between nucleotides ؊174 and ؊4 is fully responsible for the basal gene expression, whereas the region from ؊558 to ؊179 is implicated in the induction of apoD expression following growth arrest. Within this region, an alternating purine-pyrimidine stretch and a pair of serum-responsive elements (SRE) were found to be major determinants of growth arrest-induced apoD gene expression. Evidence is also presented that SREs in the apoE promoter may contribute to the up-regulation of apoE gene expression following growth arrest.

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Sequences at the 3′ Side of the c-fos SRE Mediate Gene Expression via an Sob1-Dependent, TCF-Independent Pathway

Omoike

Benson

Chan

et al. 1999

Biochemical and Biophysical Research Communications

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A Kinase/Phosphatase System Involving the Protooncogene Lck Is Necessary for Inducible Modulation of Sob 1 during T Cell Activation

Cited by 3 publications

References 0 publications

Evidence for Transcriptional Regulation of the Glucose-6-Phosphate Transporter by HIF-1α: Targeting G6PT with Mumbaistatin Analogs in Hypoxic Mesenchymal Stromal Cells

Evidence for Transcriptional Regulation of the Glucose-6-Phosphate Transporter by HIF-1α: Targeting G6PT with Mumbaistatin Analogs in Hypoxic Mesenchymal Stromal Cells

Modulation of Apolipoprotein D and Apolipoprotein E mRNA Expression by Growth Arrest and Identification of Key Elements in the Promoter

Sequences at the 3′ Side of the c-fos SRE Mediate Gene Expression via an Sob1-Dependent, TCF-Independent Pathway

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