Regulatory sequences and protein-binding sites involved in the expression of the rat plasminogen activator inhibitor-1 gene.

Johnson, Maureen; Bruzdzinski, Carolyn J.; Winograd, Sigal S.; Gelehrter, Thomas D.

doi:10.1016/s0021-9258(19)49825-6

Cited by 32 publications

(2 citation statements)

References 69 publications

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“…Next, we investigated whether ADAM9 influenced SERPINE1 gene transcription by measuring SERPINE1 promoter activity. Two repressor elements (-764 to -628 and -266 to -188) have been previously identified in the SERPINE1 promoter, but the identity of potential repressors remains unknown [28]. We linked the 5'-flanking regions of the SERPINE1 promoter at positions -1200, -600, and -300, respectively, with the luciferase gene to measure the promoter activity in control and ADAM9 KO cells (Figure 6A).…”

Section: Adam9 Suppresses Serpine1 Transcription By Interacting With Known Transcription Factors For Serpine1 Gene Regulation In Esccmentioning

confidence: 99%

ADAM9 functions as a transcriptional regulator to drive angiogenesis in esophageal squamous cell carcinoma

Lin¹,

Kuo²,

Lo³

et al. 2021

Int. J. Biol. Sci.

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Hypoxia and angiogenesis play key roles in the pathogenesis of esophageal squamous cell carcinoma (ESCC), but regulators linking these two pathways to drive tumor progression remain elusive. Here we provide evidence of ADAM9's novel function in ESCC progression. Increasing expression of ADAM9 was correlated with poor clinical outcomes in ESCC patients. Suppression of ADAM9 function diminished ESCC cell migration and in vivo metastasis in ESCC xenograft mouse models. Using cellular fractionation and imaging, we found a fraction of ADAM9 was present in the nucleus and was uniquely associated with gene loci known to be linked to the angiogenesis pathway demonstrated by genome-wide ChIP-seq. Mechanistically, nuclear ADAM9, triggered by hypoxia-induced translocation, functions as a transcriptional repressor by binding to promoters of genes involved in the negative regulation of angiogenesis, and thereby promotes tumor angiogenesis in plasminogen/plasmin pathway. Moreover, ADAM9 suppresses plasminogen activator inhibitor-1 gene transcription by interacting with its transcription factors at the promoter. Our findings uncover a novel regulatory mechanism of ADAM9 as a transcriptional regulator in angiogenesis and highlight ADAM9 as a promising therapeutic target for ESCC treatment.

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Section: Adam9 Suppresses Serpine1 Transcription By Interacting With Known Transcription Factors For Serpine1 Gene Regulation In Esccmentioning

confidence: 99%

ADAM9 functions as a transcriptional regulator to drive angiogenesis in esophageal squamous cell carcinoma

Lin¹,

Kuo²,

Lo³

et al. 2021

Int. J. Biol. Sci.

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show abstract

“…endothelial cells, but it has also been detected in cultured cells,We propose that nuclear receptors partially replace Spl in including vascular smooth muscle, granulosa, mesothelial, and homo-oligomers at the GCbox. kidney tubule cells.36 In addition, we have shown that HESCs displayed immunostaining for PAI-1 and that the decidualizing Tissue Factor effects The (RU486) to block TF-i1li-modulated transcription.3t The located at -534 bp, -85 bp, and -42 bp relative to the start TF-i1ii promoter contains three overlapping Spi and three site,39 41 we explored the possibility that this gene could be Egr-i sites.3( Site-directed mutagenesis identified the three transcriptionally regulated by these tranis-acting factors. As ob-Spi sites as the key regulators of both the constitutive and the served with TF, progestin activates PAL-i promloter activity progestin-induced activity of the TF promoter.3' Overexpres-(Krikun G, Schatz F, Lockwood GJ.…”

mentioning

confidence: 98%

Steroid Hormones, Endometrial Gene Regulation and the Sp1 Family of Proteins

Krikun

Lockwood

2002

Journal of the Society for Gynecologic Investigation

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Endometrial gene expression can be regulated exquisitely by cyclical changes in ovarian steroid concentration. Although hormonal induction of many of these genes occurs through classical steroid response elements, other endometrial genes respond to steroids at the transcriptional level but do not contain steroid response elements. A family of transcription factors, namely the Sp1 family, has now been implicated as important mediators of steroid hormone action in the endometrium during the periimplantation and postimplantation periods. This review summarizes the current literature regarding the role of the Sp1 protein family in regulating the response to steroid hormones of genes for tissue factor, plasminogen activator inhibitor-1, insulin-like growth factor binding protein-1, uteroglobin, and uteroferrin in the endometrium.

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Perturbation of the actin cytoskeleton induces PAI-1 gene expression in cultured epithelial cells independent of substrate anchorage

Providence

Kutz

Higgins

1999

Cell Motil. Cytoskeleton

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Regulatory sequences and protein-binding sites involved in the expression of the rat plasminogen activator inhibitor-1 gene.

Cited by 32 publications

References 69 publications

ADAM9 functions as a transcriptional regulator to drive angiogenesis in esophageal squamous cell carcinoma

ADAM9 functions as a transcriptional regulator to drive angiogenesis in esophageal squamous cell carcinoma

Steroid Hormones, Endometrial Gene Regulation and the Sp1 Family of Proteins

Perturbation of the actin cytoskeleton induces PAI-1 gene expression in cultured epithelial cells independent of substrate anchorage

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