Mithramycin Is a Gene-Selective Sp1 Inhibitor That Identifies a Biological Intersection between Cancer and Neurodegeneration

Langley, Brett; Basso, Manuela; Berlin, Jill; Xia, Ling; Jb, Payappilly; Mk, Kharel; H, Guo; Jl, Marsh; Lm, Thompson; Mahishi, Lata; Ahuja, Paramvir Singh; Wr, MacLellan; Dh, Geschwind; Coppola, Giovanni; Rohr, Jürgen; Rr, Ratan

doi:10.1523/jneurosci.0710-11.2011

Cited by 116 publications

(124 citation statements)

References 69 publications

Supporting

Mentioning

112

Contrasting

Order By: Relevance

“…Mithramycin A, recognized as an inhibitor of Sp1 oligonucleotide binding (37,38), also inhibited the increases in Wnt9A expression that followed carrageenan and ARSB silencing in the NCM460 cells (Fig. 7C).…”

Section: Expression Of Wnt9a Is Increased After Carrageenan or Arsb Smentioning

confidence: 84%

“…Inhibition of Sp1 Oligonucleotide Binding by Mithramycin AMithramycin A, a known inhibitor of Sp1 oligonucleotide binding (37,38), was purchased (Sigma). Control, carrageenan-exposed, and ARSB-silenced NCM460 cells were treated with mithramycin A (250 nM for 24 h), and the impact on Wnt9A expression was determined by QRT-PCR, as above.…”

Section: Arsb Galectin-3 and Sp1mentioning

confidence: 99%

See 1 more Smart Citation

Increased Expression of Colonic Wnt9A through Sp1-mediated Transcriptional Effects involving Arylsulfatase B, Chondroitin 4-Sulfate, and Galectin-3

Bhattacharyya

Feferman

Tobacman

2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Mechanism by which Wnt expression was increased by carrageenan exposure was unknown. Results: Sp1 activated Wnt9A transcription through changes in arylsulfatase B, chondroitin 4-sulfation, and galectin-3. Conclusion: Decline in arylsulfatase B leads to transcriptional effects mediated by Sp1 and galectin-3. Significance: Extracellular events can regulate transcription through changes in arylsulfatase B and chondroitin 4-sulfation.

show abstract

Section: Expression Of Wnt9a Is Increased After Carrageenan or Arsb Smentioning

confidence: 84%

Section: Arsb Galectin-3 and Sp1mentioning

confidence: 99%

Increased Expression of Colonic Wnt9A through Sp1-mediated Transcriptional Effects involving Arylsulfatase B, Chondroitin 4-Sulfate, and Galectin-3

Bhattacharyya

Feferman

Tobacman

2014

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Pretreatment of WT BMDM with mithramycin A, a specific Sp1 inhibitor, 40,41 prevented BCM-induced expression of caveolin-1 mRNA and protein (Figures 5a and b), as well as BCM reduced Mϕ surface expression of TLR4, a reflection of TLR4 internalization ( Figure 5c). …”

Section: Figure 1 Continuedmentioning

confidence: 95%

Tissue damage negatively regulates LPS-induced macrophage necroptosis

Scott

Fan

et al. 2016

Cell Death Differ

View full text Add to dashboard Cite

Infection is a common clinical complication following tissue damage resulting from surgery and severe trauma. Studies have suggested that cell pre-activation by antecedent trauma/tissue damage profoundly impacts the response of innate immune cells to a secondary infectious stimulus. Cell necroptosis, a form of regulated inflammatory cell death, is one of the mechanisms that control cell release of inflammatory mediators from important innate immune executive cells such as macrophages (Mϕ), which critically regulate the progress of inflammation. In this study, we investigated the mechanism and role of trauma/tissue damage in the regulation of LPS-induced Mϕ necroptosis using a mouse model simulating long-bone fracture. We demonstrate that LPS acting through Toll-like receptor (TLR) 4 promotes Mϕ necroptosis. However, necroptosis is ameliorated by high-mobility group box 1 (HMGB1) release from damaged tissue. We show that HMGB1 acting through cell surface receptor for advanced glycation end products (RAGE) upregulates caveolin-1 expression, which in turn induces caveolae-mediated TLR4 internalization and desensitization to decrease Mϕ necroptosis. We further show that RAGE-MyD88 activation of Cdc42 and subsequent activation of transcription factor Sp1 serves as a mechanism underlying caveolin-1 transcriptional upregulation. These results reveal a previous unidentified protective role of damage-associated molecular pattern (DAMP) molecules in restricting inflammation in response to exogenous pathogen-associated molecular pattern molecules.

show abstract

“…Based on the previous observation that MA could effectively prevent the binding of SP1 to the CAR promoter (Chung et al 2011), we blocked SP1 using MA and then observed for TNFa core promoter activity in the ERa-transfected cells. Ectopic expression of ERa enhanced TNFa promoter activity, and this promoter activity was abolished by the SP1 inhibitor (Sleiman et al 2011). These observations suggest that ERa is able to bind to TNFa in the presence of estrogen stimulation and enhance its transcription; however, deletion of the SP1 site in the TNFa promoter region blocked its transcription.…”

Section: Figurementioning

confidence: 98%

Estrogen receptor α (ESR1) over-expression mediated apoptosis in Hep3B cells by binding with SP1 proteins

Tu¹,

Velmurugan

Day

et al. 2013

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Previous studies have reported that estrogen receptors (ERs) are expressed in normal human liver, chronic hepatitis, and benign hepatic tumor tissues. However, decreased expression of ERs can be observed in hepatocellular carcinoma (HCC) and the role of ERs in HCC is not fully understood. Thus, the present study aimed to investigate the molecular mechanism induced by the overexpression of ERa (ERa (ESR1)) in Hep3B cells. We first detected the induction of apoptosis in ER-negative Hep3B cells using DNA fragmentation assay and flow cytometry. We found that ERa and ERa plus 17b-estradiol treatment increased apoptosis in Hep3B cells. Additionally, western blotting showed increased expression of active caspase 3 and tumor necrosis factor a (TNFa (TNF)) in ERa-transfected cells. To further understand the importance of SP1-binding sites in the TNFa promoter, ERa-negative Hep3B cells were co-transfected with ERa and a wild-type TNFa plasmid or TNFa with deleted SP1 regions. Deletion of both distant and primal SP1 sites abolished the activity of ERa, and similar results were observed by blocking the expression of SP1 protein using mithramycin (MA). This result indicates that SP1 protein is essential for ERa-activated TNFa promoter activity. Co-immunoprecipitation assay further confirmed the binding interaction between ERa and SP1 in a ligand-dependent manner.In general, we demonstrate that the overexpression of ERa mediates apoptosis in ERa-negative Hep3B cells by the binding of ERa to SP1 protein. Additionally, this ERa-SP1 complex binds to the proximal and distal sites of the TNFa gene promoter and further induces the expression of active caspase 3 in a ligand-dependent manner.

show abstract

Mithramycin Is a Gene-Selective Sp1 Inhibitor That Identifies a Biological Intersection between Cancer and Neurodegeneration

Cited by 116 publications

References 69 publications

Increased Expression of Colonic Wnt9A through Sp1-mediated Transcriptional Effects involving Arylsulfatase B, Chondroitin 4-Sulfate, and Galectin-3

Increased Expression of Colonic Wnt9A through Sp1-mediated Transcriptional Effects involving Arylsulfatase B, Chondroitin 4-Sulfate, and Galectin-3

Tissue damage negatively regulates LPS-induced macrophage necroptosis

Estrogen receptor α (ESR1) over-expression mediated apoptosis in Hep3B cells by binding with SP1 proteins

Contact Info

Product

Resources

About