TBL1–TBLR1 and β-catenin recruit each other to Wnt target-gene promoter for transcription activation and oncogenesis

2008 ◽  
Vol 10 (2) ◽  
pp. 160-169 ◽  
Author(s):  
Jiong Li ◽  
Cun-Yu Wang
Keyword(s):  
Target Gene ◽  
Gene Promoter ◽  
Transcription Activation ◽  
Target Gene Promoter

scholarly journals FGF18 Enhances Migration and the Epithelial-Mesenchymal Transition in Breast Cancer by Regulating Akt/GSK3β/Β-Catenin Signaling

2018 ◽  
Vol 49 (3) ◽  
pp. 1060-1073 ◽  
Author(s):  
Na Song ◽  
Jiateng Zhong ◽  
Qing Hu ◽  
Tengteng Gu ◽  
Bo Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Target Gene ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Gene Promoter ◽  
Hypoxic Condition ◽  
Mesenchymal Transition ◽  
Target Gene Promoter

Background/Aims: Fibroblast growth factors (FGFs) and their high-affinity receptors contribute to autocrine and paracrine growth stimulation in several human malignant tumors, including breast cancer. However, the mechanisms underlying the carcinogenic actions of FGF18 remain unclear. Methods: The transcription level of FGF18 under the hypoxic condition was detected with quantitative PCR (qPCR). A wound-healing assay was performed to assess the role of FGF18 in cell migration. A clonogenicity assay was used to determine whether FGF18 silencing affected cell clonogenicity. Western blotting was performed to investigate Akt/GSK3β/β-catenin pathway protein expression. Binding of β-catenin to the target gene promoter was determined by chromatin immunoprecipitation (ChIP) assays. Results: FGF18 promoted the epithelial-mesenchymal transition (EMT) and migration in breast cancer cells through activation of the Akt/GSK3β/β-catenin pathway. FGF18 increased Akt-Ser473 and -Thr308 phosphorylation, as well as that of GSK3β-Ser9. FGF18 also enhanced the transcription of proliferation-related genes (CDK2, CCND2, Ki67), metastasis-related genes (TGF-β, MMP-2, MMP-9), and EMT markers (Snail-1, Snail-2, N-cadherin, vimentin, TIMP1). β-catenin bound to the target gene promoter on the ChIP assay. Conclusion: FGF18 contributes to the migration and EMT of breast cancer cells following activation of the Akt/GSK3β/β-catenin pathway. FGF18 expression may be a potential prognostic therapeutic marker for breast cancer.

Isolation of Target Gene Promoter/Enhancer Sequences by Whole Genome PCR Method

2003 ◽  
pp. 1-12
Author(s):  
Dennis K. Watson ◽  
Richard Kitching ◽  
Calvin Vary ◽  
Ismail Kola ◽  
Arun Seth
Keyword(s):  
Target Gene ◽  
Gene Promoter ◽  
Whole Genome ◽  
Target Gene Promoter ◽  
Pcr Method ◽  
Enhancer Sequences

scholarly journals ACE-2/ANG1-7 ameliorates ER stress-induced apoptosis in seawater aspiration-induced acute lung injury

2018 ◽  
Vol 315 (6) ◽  
pp. L1015-L1027 ◽  
Author(s):  
MinLong Zhang ◽  
Yongheng Gao ◽  
Weiguo Zhao ◽  
Gaole Yu ◽  
Faguang Jin
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Er Stress ◽  
Target Gene ◽  
Active Form ◽  
Gene Promoter ◽  
Ang Ii ◽  
Alveolar Cells ◽  
Target Gene Promoter ◽  
Induced Apoptosis

Previous studies have shown that apoptosis of alveolar cells can be regulated by autocrine of angiotensin (ANG)II and its counter regulatory ACE-2/ANG1-7 axis. Our earlier study has shown that endoplasmic reticulum (ER) stress in response to seawater aspiration eventually led to apoptosis in lung tissue. In this study, we examined the hypothesis that ER stress-induced apoptosis in seawater aspiration-induced acute lung injury (ALI) might also be regulated by the ANGII/ANG1-7 system. ER stress was induced by seawater stimulation and proteasome inhibitor MG132 (an ER stress inductor). Moreover, ER stress in seawater-stimulated lung tissues and rat pulmonary microvascular endothelial cells (RPMVECs) promoted ANGII expression and decreased ACE-2/ANG1-7 expression. ER stress induced by seawater stimulation also led to apoptosis. Apoptosis induced by seawater stimulation and MG132 were inhibited by ANGII receptor blocker and abrogated by the addition of ANG1-7. These results suggest that apoptosis induced by ER stress in seawater aspiration-induced ALI is regulated by ANG II/ANG1-7 in lung tissues and RPMVECs. In addition, the active form of X-box binding protein 1 (XBP1), spliced XBP1 (XBP1s), a transcription factor that regulates ER-associated degradation genes during ER stress was significantly activated in seawater stimulated cells. Based on this phenomenon we designed a tandem gene, Wfs1 promoter (a target gene promoter of XBP1s)- ACE2 and ANG1-7 and transfected this tandem gene into seawater-stimulated cells. ACE-2/ANG1-7 expression were significantly promoted and apoptosis was inhibited in cells transfected with the tandem gene. These results suggest that stimulation of ACE-2/ANG1-7 may be a therapeutic target of ER stress-induced apoptosis in seawater aspiration-induced ALI.

scholarly journals Hsp90 inhibition suppresses NF-κB transcriptional activation via Sirt-2 in human lung microvascular endothelial cells

2016 ◽  
Vol 310 (10) ◽  
pp. L964-L974 ◽  
Author(s):  
Gagan S. Thangjam ◽  
Charalampos Birmpas ◽  
Nektarios Barabutis ◽  
Betsy W. Gregory ◽  
Mary Ann Clemens ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Transcriptional Activation ◽  
Target Gene ◽  
Molecular Mechanisms ◽  
Human Lung ◽  
Gene Promoter ◽  
Microvascular Endothelial Cells ◽  
Mrna Induction ◽  
Target Gene Promoter ◽  
Microvascular Endothelial

The ability of anti-heat shock protein 90 (Hsp90) drugs to attenuate NF-κB-mediated transcription is the major basis for their anti-inflammatory properties. While the molecular mechanisms underlying this effect are not clear, they appear to be distinct in human endothelial cells. We now show for the first time that type 2 sirtuin (Sirt-2) histone deacetylase binds human NF-κB target gene promoter and prevents the recruitment of NF-κB proteins and subsequent assembly of RNA polymerase II complex in human lung microvascular endothelial cells. Hsp90 inhibitors stabilize the Sirt-2/promoter interaction and impose a “transcriptional block,” which is reversed by either inhibition or downregulation of Sirt-2 protein expression. Furthermore, this process is independent of NF-κB (p65) Lysine 310 deacetylation, suggesting that it is distinct from known Sirt-2-dependent mechanisms. We demonstrate that Sirt-2 is recruited to NF-κB target gene promoter via interaction with core histones. Upon inflammatory challenge, chromatin remodeling and core histone H3 displacement from the promoter region removes Sirt-2 and allows NF-κB/coactivator recruitment essential for RNA Pol II-dependent mRNA induction. This novel mechanism may have important implications in pulmonary inflammation.

c-myc reverses neu-induced transformed morphology by transcriptional repression

1991 ◽  
Vol 11 (1) ◽  
pp. 354-362
Author(s):  
T C Suen ◽  
M C Hung
Keyword(s):  
Transcriptional Repression ◽  
Target Gene ◽  
Gene Promoter ◽  
Transformation Process ◽  
Breast Cancers ◽  
Cellular Target ◽  
Normal Rat ◽  
Neu Oncogene ◽  
Nih 3T3 ◽  
Positive Factor

Amplification or overexpression or both of either the c-myc or the human neu (C-erbB-2) gene are common events in many primary human tumors. Coamplification or overexpression or both of both genes have been reported in some breast cancers. The possibility of cooperation between the c-myc and the normal rat neu (c-neu) genes in transforming cells was examined. Surprisingly, the expression of c-myc in B104-1-1 cells, and activated rat neu oncogene (neu*)-transformed NIH 3T3 line, resulted in morphologic reversion. This reversion was found to be a consequence of a transcription-repressive action of c-myc on the neu gene via a 140-bp fragment on the neu gene promoter. The effective concentration of a positive factor(s) interacting with this fragment seemed to be lowered by the expression of c-myc. Our findings lend support to arguments concerning the long-suspected function of c-myc as a transcriptional modulator. They also imply that an oncogene such as c-myc, or possibly the rapidly explored class that encodes transcription factors, under certain conditions may act to reverse a transformed phenotype that is induced by another oncogene instead of contributing positively towards the transformation process. Therefore, the activity of an oncogene may depend on the environment in which it is expressed. In addition, we may have identified the neu gene as a cellular target gene of negative regulation by c-myc.

scholarly journals Elongation Inhibition by DRB Sensitivity-Inducing Factor Is Regulated by the A20 Promoter via a Novel Negative Element and NF-κB

2004 ◽  
Vol 24 (6) ◽  
pp. 2444-2454 ◽  
Author(s):  
Elena Ainbinder ◽  
Liat Amir-Zilberstein ◽  
Yuki Yamaguchi ◽  
Hiroshi Handa ◽  
Rivka Dikstein
Keyword(s):  
Target Gene ◽  
Cultured Cells ◽  
Transcription Activation ◽  
Differential Regulation ◽  
Promoter Element ◽  
Potential Significance ◽  
Negative Element ◽  
Dynamic Relationship ◽  
Upstream Promoter

ABSTRACT A20 is an immediate-early NF-κB target gene. Prior to NF-κB stimulation, the A20 promoter is bound by the polymerase II machinery to allow rapid transcription activation. Here we show that the basal A20 transcription is repressed at the level of elongation in a promoter-specific fashion. Immunodepletion in vitro and RNA interference in cultured cells suggest that the basal elongation inhibition is conferred by DRB sensitivity-inducing factor (DSIF). We have identified a negative upstream promoter element called ELIE that controls DSIF activity. Remarkably, following NF-κB stimulation, inhibition of the A20 promoter by DSIF persists, but it is now regulated by NF-κB rather than ELIE. Similar regulation by DSIF is shown for another NF-κB-responsive gene, the IκBα gene. These findings reveal an intimate and dynamic relationship between DSIF inhibition of elongation and promoter-bound transcription factors. The potential significance of the differential regulation of DSIF activity by cis-acting elements is discussed.

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