Mithramycin blocks protein binding and function of the SV40 early promoter.

Ray, Ratna B.; Snyder, Richard C.; Thomas, Shelia D.; Koller, Charles; Miller, Donald M.

doi:10.1172/jci114110

Cited by 134 publications

(111 citation statements)

References 30 publications

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“…We blocked the activity of CREB and SP1 by using respectively, ICER, a dominant negative form of CREB, and mithramycin A, a drug that inhibits the activity of the transcription factors of the SP1 family. 28,29 Separately, ICER and mithramycin reduced by approximately 50% the induction of the spry2 promoter by BDNF, whereas Figure 3d). These results suggest that BDNF stimulates spry2 expression by regulating its promoter through cooperation between CREB and SP1.…”

Section: Resultsmentioning

confidence: 88%

Sprouty2 inhibits BDNF-induced signaling and modulates neuronal differentiation and survival

Groß

Armant²,

Benosman

et al. 2007

Cell Death Differ

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Sprouty (Spry) proteins are ligand-inducible inhibitors of receptor tyrosine kinases-dependent signaling pathways, which control various biological processes, including proliferation, differentiation and survival. Here, we investigated the regulation and the role of Spry2 in cells of the central nervous system (CNS). In primary cultures of immature neurons, the neurotrophic factor BDNF (brain-derived neurotrophic factor) regulates spry2 expression. We identified the transcription factors CREB and SP1 as important regulators of the BDNF activation of the spry2 promoter. In immature neurons, we show that overexpression of wildtype Spry2 blocks neurite formation and neurofilament light chain expression, whereas inhibition of Spry2 by a dominantnegative mutant or small interfering RNA favors sprouting of multiple neurites. In mature neurons that exhibit an extensive neurite network, spry2 expression is sustained by BDNF and is downregulated during neuronal apoptosis. Interestingly, in these differentiated neurons, overexpression of Spry2 induces neuronal cell death, whereas its inhibition favors neuronal survival. Together, our results imply that Spry2 is involved in the development of the CNS by inhibiting both neuronal differentiation and survival through a negative-feedback loop that downregulates neurotrophic factors-driven signaling pathways.

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Section: Resultsmentioning

confidence: 88%

Sprouty2 inhibits BDNF-induced signaling and modulates neuronal differentiation and survival

Groß

Armant²,

Benosman

et al. 2007

Cell Death Differ

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“…This resulted in gel retardation in comparison with the free DNA probe which served as a negative control ( Fig. 2A) under nondenaturing, low-ionicstrength polyacrylamide gel electrophoresis (54,58). The recombinant protein from the bacterial extract bound to the 142-bp c-myc P2 DNA fragment and formed protein-DNA complexes ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…DNase I footprinting analysis of the human c-myc P2 fragment with MBP-1 was performed as previously described (54). In brief, the radiolabeled fragment was incubated with crude bacterial extract for 20 min at room temperature.…”

mentioning

confidence: 99%

Cloning and characterization of a human c-myc promoter-binding protein.

Ray¹,

Miller²

1991

Mol. Cell. Biol.

Self Cite

107

128

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A human cDNA clone encoding a c-myc promoter-binding protein was detected by screening a HeLa cell k phage expression cDNA library. The library was screened by using an XhoI-NaeI human c-myc P2 promoter fragment as a probe. The recombinant phage encoded a fusion protein, myc-binding protein 1 (MBP-1), which had an apparent molecular size of 40 kDa. A corresponding protein with a molecular size of 35 kDa was present in a HeLa cell extract. Sequence analysis of the cloned gene reveals an open reading frame of 1,038 bp with a 3' untranslated region of 378 bp. The predicted protein sequence contains a proline-rich region in the amino terminus but does not demonstrate a known DNA-binding domain. DNase I footprint analysis demonstrates that MBP-1 binds to the sequence just 5' of the TATA box sequence of the human c-myc P2 promoter. MBP-1 cDNA hybridizes to a 1.4-kb mRNA from HeLa and HL-60 cells, indicating that the cDNA insert (1,416 bp) is a full-length clone. Coexpression of the MBP-1 protein represses transcription from the human c-myc promoter, suggesting that MBP-1 may act as a negative regulatory factor for the human c-myc gene.

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“…12A). Mithramycin A binds to the GC box in DNA, thereby inhibiting the binding of Sp1 to its binding site (38,39). The treatment of A549 cells with mithramycin A resulted in reduced promoter activity of the ␤-1,4-GalT V gene (Fig.…”

Section: Identification Of Transcription Factorsmentioning

confidence: 99%