The N-Terminal Domain of the Mineralocorticoid Receptor Modulates both Mineralocorticoid Receptor- and Glucocorticoid Receptor-Mediated Transactivation from Na/K ATPase β1 Target Gene Promoter

Endocrine ◽  
2000 ◽  
Vol 13 (3) ◽  
pp. 287-295 ◽  
Author(s):  
Assia Derfoul ◽  
Noreen M. Robertson ◽  
David J. Hall ◽  
Gerald Litwack
Keyword(s):  
Glucocorticoid Receptor ◽  
Mineralocorticoid Receptor ◽  
Target Gene ◽  
Gene Promoter ◽  
Terminal Domain ◽  
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.

scholarly journals N-terminal Domain Regulates Steroid Activation of Elephant Shark Glucocorticoid and Mineralocorticoid Receptors

2019 ◽  
Author(s):  
Yoshinao Katsu ◽  
Islam MD Shariful ◽  
Xiaozhi Lin ◽  
Wataru Takagi ◽  
Hiroshi Urushitani ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Mineralocorticoid Receptor ◽  
Functional Divergence ◽  
Full Length ◽  
Mineralocorticoid Receptors ◽  
Elephant Shark ◽  
Terminal Domain ◽  
Cartilaginous Fishes ◽  
Steroid Binding

AbstractOrthologs of human glucocorticoid receptor (GR) and human mineralocorticoid receptor (MR) first appear in cartilaginous fishes. Subsequently, the MR and GR diverged to respond to different steroids: the MR to aldosterone and the GR to cortisol and corticosterone. We report that cortisol, corticosterone and aldosterone activate full-length elephant shark GR, and progesterone, which activates elephant shark MR, does not activate elephant shark GR. However, progesterone inhibits steroid binding to elephant shark GR, but not to human GR. Together, this indicates partial functional divergence of elephant shark GR from the MR. Deletion of the N-terminal domain (NTD) from elephant shark GR (truncated GR) reduced the response to corticosteroids, while truncated and full-length elephant shark MR had similar responses to corticosteroids. Swapping of NTDs of elephant shark GR and MR yielded an elephant shark MR chimera with full-length GR-like increased activation by corticosteroids and progesterone compared to full-length elephant shark MR. Elephant shark MR NTD fused to GR DBD+LBD had similar activation as full-length MR, indicating that the MR NTD lacked GR-like NTD activity. We propose that NTD activation of human GR evolved early in GR divergence from the MR.

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 N-terminal Domain Regulates Steroid Activation of Elephant Shark Glucocorticoid and Mineralocorticoid Receptors

2020 ◽  
Author(s):  
Yoshinao Katsu ◽  
Islam MD Shari ◽  
Xiaozhi Lin ◽  
Wataru Takagi ◽  
Hiroshi Urushitani ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Mineralocorticoid Receptor ◽  
Functional Divergence ◽  
Full Length ◽  
Mineralocorticoid Receptors ◽  
Elephant Shark ◽  
Terminal Domain ◽  
Cartilaginous Fishes ◽  
Steroid Binding

Abstract Orthologs of human glucocorticoid receptor (GR) and human mineralocorticoid receptor (MR) first appear in cartilaginous fishes. Subsequently, the MR and GR diverged to respond to different steroids: the MR to aldosterone and the GR to cortisol and corticosterone. We report that cortisol, corticosterone and aldosterone activate full-length elephant shark GR, and progesterone, which activates elephant shark MR, does not activate elephant shark GR. However, progesterone inhibits steroid binding to elephant shark GR, but not to human GR. Together, this indicates partial functional divergence of elephant shark GR from the MR. Deletion of the N-terminal domain (NTD) from elephant shark GR (truncated GR) reduced the response to corticosteroids, while truncated and full-length elephant shark MR had similar responses to corticosteroids. Swapping of NTDs of elephant shark GR and MR yielded an elephant shark MR chimera with full-length GR-like increased activation by corticosteroids and progesterone compared to full-length elephant shark MR. Elephant shark MR NTD fused to GR DBD+LBD had similar activation as full-length MR, indicating that the MR NTD lacked GR-like NTD activity. We propose that NTD activation of human GR evolved early in GR divergence from the MR.

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.

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