A Sp1 Binding Site of the Tumor Necrosis Factor α Promoter Functions as a Nitric Oxide Response Element

Wang, Shuibang; Wang, Weihan; Wesley, Robert; Danner, Robert L.

doi:10.1074/jbc.274.47.33190

Cited by 76 publications

(79 citation statements)

References 31 publications

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“…Deletion or site-directed mutagenesis of this canonical CDE/CHR sequence entirely eliminated the NO ⅐ effect. This experimental evidence also excludes the possibility that NO ⅐ down-regulated PLK1 transcription through a nearby Sp1 site in the PLK1 promoter, a mechanism of NO ⅐ -mediated regulation that has been demonstrated for other genes (12,13).…”

Section: Discussionmentioning

confidence: 94%

“…Reporter Gene Assays-The two-plasmid reporter gene system used in this investigation has been described previously (12,13). Briefly, promoters of interest were inserted into the first plasmid, promoterless ptTA, to induce production of a trans-activator (tTA) containing a tetracycline response element binding domain.…”

Section: Methodsmentioning

confidence: 99%

“…Nitric oxide (NO ⅐ ) regulates a wide range of cellular activities including gene expression (12)(13)(14)(15)(16), cell proliferation (17,18), and apoptosis (19) that are closely linked to its anti-tumor and anti-atherosclerotic properties (17,20). Using a microarraybased approach in soluble guanylate cyclase-deficient cells, we recently demonstrated that NO ⅐ predominately regulated a large set of cell cycle genes independent cGMP (15).…”

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confidence: 99%

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Nitric Oxide Down-regulates Polo-like Kinase 1 through a Proximal Promoter Cell Cycle Gene Homology Region

Zhang

Wang

Kern

et al. 2007

Journal of Biological Chemistry

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Polo-like kinase 1 (PLK1) is an evolutionarily conserved serine/threonine kinase essential for cell mitosis. As a master cell cycle regulator, p21/Waf1 plays a critical role in cell cycle progression. Nitric oxide (NO ⅐ ) has been shown to down-regulate PLK1 and up-regulate p21/Waf1 independent of cGMP. Here, the respective roles of p38 MAPK and p21/Waf1 in NO ⅐ -mediated PLK1 repression were investigated using differentiated U937 cells that lack soluble guanylate cyclase. NO ⅐ was shown to down-regulate both PLK1 mRNA and protein. Nuclear run-on assays and mRNA stability studies demonstrated that the effect of NO ⅐ on PLK1 expression was associated with decreased transcription without changes in transcript stability. SB202190, a p38 MAPK inhibitor, prevented transcriptional repression of PLK1 by NO ⅐ . Transfection with dominant-negative p38 MAPK mutant eliminated the NO ⅐ effect on both p21/Waf1 and PLK1 gene expression. Knockdown of p21/Waf1 with siRNA also substantially reduced the regulatory effect of NO ⅐ on PLK1. Reporter gene experiments showed that NO ⅐ decreased activity of the PLK1 proximal promoter, an effect that was blocked by p38 MAPK inhibitor. Deletion or mutation of the CDE/CHR promoter site, an element regulated by p21/Waf1, increased base-line promoter activity and abolished NO ⅐ repression of the PLK1 promoter. Likewise, electrophoretic mobility shift assays with CDE/CHR probe revealed a NO ⅐ -mediated change in protein-probe complex formation. Competition with various unlabeled CDE/CHR mutant sequences showed that NO ⅐ increased nuclear protein binding to intact CHR. These results demonstrate that a NO ⅐ -p38 MAPK-p21/Waf1 signal transduction pathway represses PLK1 through a canonical CDE/CHR promoter element.

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Section: Discussionmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

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confidence: 99%

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Nitric Oxide Down-regulates Polo-like Kinase 1 through a Proximal Promoter Cell Cycle Gene Homology Region

Zhang

Wang

Kern

et al. 2007

Journal of Biological Chemistry

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“…EGR-1 and SP-1; Ahmed et al, 1997;Wang et al, 1999;Raju et al, 2000). Both ROS and RNS inhibit DNA binding of zinc-finger transcription factors by stimulating the release of the metal ion.…”

Section: Transcription Factors As Ros/rns Sensorsmentioning

confidence: 99%

Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms

2003

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In the past few years, nuclear DNA damage-sensing mechanisms activated by ionizing radiation have been identified, including ATM/ATR and the DNA-dependent protein kinase. Less is known about sensing mechanisms for cytoplasmic ionization events and how these events influence nuclear processes. Several studies have demonstrated the importance of cytoplasmic signaling pathways in cytoprotection and mutagenesis. For cytoplasmic signaling, radiation-stimulated reactive oxygen species (ROS) and reactive nitrogen species (RNS) are essential activators of these pathways. This review summarizes recent studies on the chemistry of radiation-induced ROS/ RNS generation and emphasizes interactions between ROS and RNS and the relative roles of cellular ROS/ RNS generators as amplifiers of the initial ionization events. Cellular mechanisms for regulating ROS/RNS levels are discussed. The mechanisms by which cells sense ROS/RNS are examined in terms of how ROS/RNS modify protein structure and function, for example, interactions with metal-thiol clusters, protein tyrosine nitration, protein cysteine oxidation, S-thiolation and Snitrosylation. We propose that radiation-induced ROS are the initiators and that nitric oxide (NO ) or derivatives are the effectors activating these signal transduction pathways. In responding to cellular ionization events, the cell converts an oxidative signal to a nitrosative one because ROS are too reactive and unspecific in their reactions for regulatory purposes and the cell is equipped to precisely modulate NO levels.

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“…Likewise the promoter of the TNF-a gene is also under the control of Sp1 factors. 21 Transcription factor Sp1 binds to the GC box, which can be found in the promoter region of a variety of constitutive and inducible mammalian genes. [22][23][24][25][26] Although Sp1 binding has been shown to activate gene transcription, 25 for some genes, Sp1 acts as a repressor.…”

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confidence: 99%

Downregulation of TNF-α and VEGF expression by Sp1 decoy oligodeoxynucleotides in mouse melanoma tumor

et al. 2003

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A Sp1 Binding Site of the Tumor Necrosis Factor α Promoter Functions as a Nitric Oxide Response Element

Abstract: Regulation of gene transcription is an incompletely understood function of nitric oxide (NO).

Cited by 76 publications

References 31 publications

Nitric Oxide Down-regulates Polo-like Kinase 1 through a Proximal Promoter Cell Cycle Gene Homology Region

Nitric Oxide Down-regulates Polo-like Kinase 1 through a Proximal Promoter Cell Cycle Gene Homology Region

Biological chemistry of reactive oxygen and nitrogen and radiation-induced signal transduction mechanisms

Downregulation of TNF-α and VEGF expression by Sp1 decoy oligodeoxynucleotides in mouse melanoma tumor

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