scholarly journals Identification of a cAMP response element within the glucose- 6-phosphatase hydrolytic subunit gene promoter which is involved in the transcriptional regulation by cAMP and glucocorticoids in H4IIE hepatoma cells

1999 ◽  
Vol 338 (2) ◽  
pp. 457 ◽  
Author(s):  
Dieter SCHMOLL ◽  
Christina WASNER ◽  
Carolyn J. HINDS ◽  
Bernard B. ALLAN ◽  
Reinhard WALTHER ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Gene Promoter ◽  
Hepatoma Cells ◽  
Subunit Gene ◽  
Camp Response Element ◽  
Response Element

scholarly journals Identification of a cAMP response element within the glucose- 6-phosphatase hydrolytic subunit gene promoter which is involved in the transcriptional regulation by cAMP and glucocorticoids in H4IIE hepatoma cells

1999 ◽  
Vol 338 (2) ◽  
pp. 457-463 ◽  
Author(s):  
Dieter SCHMOLL ◽  
Christina WASNER ◽  
Carolyn J. HINDS ◽  
Bernard B. ALLAN ◽  
Reinhard WALTHER ◽  
...  
Keyword(s):  
Reporter Gene ◽  
Consensus Sequence ◽  
Gene Promoter ◽  
Hepatoma Cells ◽  
Luciferase Reporter ◽  
Regulation Of Transcription ◽  
Dibutyryl Camp ◽  
Luciferase Reporter Gene ◽  
Camp Response Element ◽  
Response Element

The expression of a luciferase reporter gene under the control of the human glucose 6-phosphatase gene promoter was stimulated by both dexamethasone and dibutyryl cAMP in H4IIE hepatoma cells. A cis-active element located between nucleotides -161 and -152 in the glucose 6-phosphatase gene promoter was identified and found to be necessary for both basal reporter-gene expression and induction of expression by both dibutyryl cAMP and dexamethasone. Nucleotides -161 to -152 were functionally replaced by the consensus sequence for a cAMP response element. An antibody against the cAMP response element-binding protein caused a supershift in gel-electrophoretic-mobility-shift assays using an oligonucleotide probe representing the glucose 6-phosphatase gene promoter from nucleotides -161 to -152. These results strongly indicate that in H4IIE cells the glucose 6-phosphatase gene-promoter sequence from -161 to -152 is a cAMP response element which is important for the regulation of transcription of the glucose 6-phosphatase gene by both cAMP and glucocorticoids.

scholarly journals HBP1-mediated transcriptional repression of AFP inhibits hepatoma progression

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Zhengyi Cao ◽  
Yuning Cheng ◽  
Jiyin Wang ◽  
Yujuan Liu ◽  
Ruixiang Yang ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Transcriptional Repression ◽  
Chinese Herb ◽  
Gene Promoter ◽  
Hepatoma Cells ◽  
Luciferase Assay ◽  
B Virus ◽  
And Migration ◽  
Induced Apoptosis ◽  
Common Malignancy

Abstract Background Hepatoma is a common malignancy of the liver. The abnormal high expression of alpha-fetoprotein (AFP) is intimately associated with hepatoma progress, but the mechanism of transcriptional regulation and singularly activation of AFP gene in hepatoma is not clear. Methods The expression of transcription factor HBP1 and AFP and clinical significance were further analyzed in hepatoma tissues from the patients who received surgery or TACE and then monitored for relapse for up 10 years. HBP1-mediated transcriptional regulation of AFP was analyzed by Western blotting, Luciferase assay, Realtime-PCR, ChIP and EMSA. After verified the axis of HBP-AFP, its impact on hepatoma was measured by MTT, Transwell and FACS in hepatoma cells and by tumorigenesis in HBP1−/− mice. Results The relative expressions of HBP1 and AFP correlated with survival and prognosis in hepatoma patients. HBP1 repressed the expression of AFP gene by directly binding to the AFP gene promoter. Hepatitis B Virus (HBV)-encoded protein HBx promoted malignancy in hepatoma cells through binding to HBP1 directly. Icaritin, an active ingredient of Chinese herb epimedium, inhibited malignancy in hepatoma cells through enhancing HBP1 transrepression of AFP. The repression of AFP by HBP1 attenuated AFP effect on PTEN, MMP9 and caspase-3, thus inhibited proliferation and migration, and induced apoptosis in hepatoma cells. The deregulation of AFP by HBP1 contributed to hepatoma progression in mice. Conclusions Our data clarify the mechanism of HBP1 in inhibiting the expression of AFP and its suppression in malignancy of hepatoma cells, providing a more comprehensive theoretical basis and potential solutions for the diagnosis and treatment of hepatoma.

A pleiotropic element in the medium-chain acyl coenzyme A dehydrogenase gene promoter mediates transcriptional regulation by multiple nuclear receptor transcription factors and defines novel receptor-DNA binding motifs

1994 ◽  
Vol 14 (7) ◽  
pp. 4360-4372
Author(s):  
M E Carter ◽  
T Gulick ◽  
D D Moore ◽  
D P Kelly
Keyword(s):  
Transcriptional Regulation ◽  
Nuclear Receptor ◽  
Receptor Binding ◽  
Gene Promoter ◽  
Response Element ◽  
Binding Motifs ◽  
Receptor Response ◽  
Dehydrogenase Gene ◽  
Chain Acyl ◽  
Acyl Coenzyme A

We previously identified a complex regulatory element in the medium-chain acyl coenzyme A dehydrogenase gene promoter that confers transcriptional regulation by the retinoid receptors RAR and RXR and the orphan nuclear receptor HNF-4. In this study we demonstrate a trans-repressing regulatory function for the orphan receptor COUP-TF at this same nuclear receptor response element (NRRE-1). The transcriptional regulatory properties and receptor binding sequences of each nuclear receptor response element within NRRE-1 are also characterized. NRRE-1 consists of four potential nuclear hormone receptor hexamer binding sites, arranged as [<--1-(n)s-2-->-3-->(n)4<--4], three of which are used in alternative pairwise binding by COUP-TF and HNF-4 homodimers and by RAR-RXR heterodimers, as demonstrated by mobility shift assays and methylation interference analysis. Binding and transactivation studies with mutant NRRE-1 elements confirmed the existence of distinct retinoid, COUP-TF, and HNF-4 response elements that define novel receptor binding motifs: COUP-TF homodimers bound sites 1 and 3 (two hexamer repeat sequences arranged as an everted imperfect repeat separated by 14 bp or ER14), RAR-RXR heterodimers bound sites 1 and 2 (ER8), and HNF-4 homodimers bound sites 2 and 3 (imperfect DR0). Mixing cotransfection experiments demonstrated that the nuclear receptor dimers compete at NRRE-1 to modulate constitutive and ligand-mediated transcriptional activity. These data suggest a mechanism for the transcriptional modulation of genes encoding enzymes involved in cellular metabolism.

scholarly journals A pleiotropic element in the medium-chain acyl coenzyme A dehydrogenase gene promoter mediates transcriptional regulation by multiple nuclear receptor transcription factors and defines novel receptor-DNA binding motifs.

1994 ◽  
Vol 14 (7) ◽  
pp. 4360-4372 ◽  
Author(s):  
M E Carter ◽  
T Gulick ◽  
D D Moore ◽  
D P Kelly
Keyword(s):  
Transcriptional Regulation ◽  
Nuclear Receptor ◽  
Receptor Binding ◽  
Gene Promoter ◽  
Response Element ◽  
Binding Motifs ◽  
Receptor Response ◽  
Dehydrogenase Gene ◽  
Chain Acyl ◽  
Acyl Coenzyme A

We previously identified a complex regulatory element in the medium-chain acyl coenzyme A dehydrogenase gene promoter that confers transcriptional regulation by the retinoid receptors RAR and RXR and the orphan nuclear receptor HNF-4. In this study we demonstrate a trans-repressing regulatory function for the orphan receptor COUP-TF at this same nuclear receptor response element (NRRE-1). The transcriptional regulatory properties and receptor binding sequences of each nuclear receptor response element within NRRE-1 are also characterized. NRRE-1 consists of four potential nuclear hormone receptor hexamer binding sites, arranged as [<--1-(n)s-2-->-3-->(n)4<--4], three of which are used in alternative pairwise binding by COUP-TF and HNF-4 homodimers and by RAR-RXR heterodimers, as demonstrated by mobility shift assays and methylation interference analysis. Binding and transactivation studies with mutant NRRE-1 elements confirmed the existence of distinct retinoid, COUP-TF, and HNF-4 response elements that define novel receptor binding motifs: COUP-TF homodimers bound sites 1 and 3 (two hexamer repeat sequences arranged as an everted imperfect repeat separated by 14 bp or ER14), RAR-RXR heterodimers bound sites 1 and 2 (ER8), and HNF-4 homodimers bound sites 2 and 3 (imperfect DR0). Mixing cotransfection experiments demonstrated that the nuclear receptor dimers compete at NRRE-1 to modulate constitutive and ligand-mediated transcriptional activity. These data suggest a mechanism for the transcriptional modulation of genes encoding enzymes involved in cellular metabolism.

scholarly journals Estradiol Suppresses Phosphorylation of Cyclic Adenosine 3′,5′-Monophosphate Response Element Binding Protein (CREB) in the Pituitary: Evidence for Indirect Action via Gonadotropin-Releasing Hormone

1999 ◽  
Vol 13 (8) ◽  
pp. 1338-1352
Author(s):  
W. Rachel Duan ◽  
Jennifer L. Shin ◽  
J. Larry Jameson
Keyword(s):  
Gene Promoter ◽  
Camp Response Element Binding ◽  
Ovariectomized Rats ◽  
Pituitary Cells ◽  
Camp Response Element ◽  
Similar Reduction ◽  
Response Element ◽  
Creb Phosphorylation ◽  
Element Binding Protein ◽  
Phosphorylated Creb

Abstract Estradiol acts on the hypothalamus and pituitary gland to modulate the synthesis and secretion of gonadotropins. We recently reported that GnRH-induced transcription of the human gonadotropin α-gene promoter is increased markedly in transfected pituitary cells derived from animals treated with estradiol. Because the cAMP response element binding (CREB) protein plays an important role in the transcriptional regulation of this promoter and is highly regulated by posttranslational phosphorylation, we hypothesized that it might serve as a target for estradiol-induced sensitivity to GnRH. In this study, we assessed the roles of estradiol and GnRH in the regulation of CREB phosphorylation in the rat pituitary. Using an antibody that specifically recognizes phosphorylated CREB (pCREB), we found that the pituitary content of pCREB was inversely related to the level of estradiol during the estrous cycle. Ovariectomy increased the level of pCREB, and treatment with estradiol for 10 days decreased the content of pCREB dramatically (93% inhibition). A similar reduction of pCREB was seen when ovariectomized rats were treated with a GnRH receptor antagonist for 10 days. This result indicates that the ovariectomy-induced increase in pCREB is GnRH-dependent. In αT3 gonadotrope cells, estradiol had no direct effect on CREB phosphorylation, whereas GnRH increased CREB phosphorylation 4- to 5-fold within 5 min. We conclude that estradiol inhibits CREB phosphorylation in the gonadotrope, probably by inhibiting GnRH production. The estradiol-induced decrease in CREB phosphorylation is proposed to lower basalα -promoter activity and increase its responsiveness to GnRH. (Molecular Endocrinology 13: 1338–1352, 1999)

scholarly journals Transcriptional regulation of STAT3 by SPTBN1 and SMAD3 in HCC through cAMP-response element-binding proteins ATF3 and CREB2

2014 ◽  
Vol 35 (11) ◽  
pp. 2393-2403 ◽  
Author(s):  
Ling Lin ◽  
Zhixing Yao ◽  
Krithika Bhuvaneshwar ◽  
Yuriy Gusev ◽  
Bhaskar Kallakury ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Binding Proteins ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element

scholarly journals HBP1-mediated transcriptional regulation of AFP and its impact on hepatoma

2020 ◽  
Author(s):  
Zhengyi Cao ◽  
Yuning Cheng ◽  
Jiyin Wang ◽  
Yujuan Liu ◽  
Ruixiang Yang ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Caspase 3 ◽  
Chinese Herb ◽  
Gene Promoter ◽  
Hepatoma Cells ◽  
Luciferase Assay ◽  
B Virus ◽  
And Migration ◽  
Common Malignancy ◽  
Proliferation And Migration

Abstract Background: Hepatoma is a common malignancy of the liver. The abnormal high expression of alpha-fetoprotein (AFP) is intimately associated with hepatoma progress, but the mechanism of transcriptional regulation and singularly activation of AFP gene in hepatoma is not clear. Methods: The expression of transcription factor HBP1 and AFP and clinical significance were father analyzed in hepatoma tissues from the patients who received surgery or TACE and then monitored for relapse for up 10 years. HBP1-mediated transcriptional regulation of AFP was analyzed by Western blotting, luciferase assay, Realtime-PCR, ChIP and EMSA. After verified the axis of HBP-AFP, its impact on hepatoma was measured by MTT, Transwell and FACS in hepatoma cells and by tumorigenesis in HBP1-/- mice.Results: This study demonstrated that the relative expressions of HBP1 and AFP correlated with decreased survival and prognosis in hepatoma patients. HBP1 represses the expression of AFP gene by directly binding to the AFP gene promoter. Hepatitis B Virus (HBV)-encoded protein HBx promotes malignancy in hepatoma cells through binding to HBP1 directly. Icaritin, an active ingredient of Chinese herb epimedium, inhibits malignancy in hepatoma cells through enhancing HBP1 transrepression of AFP. The repression of AFP by HBP1 attenuates AFP effect on PTEN, MMP9 and caspase-3, thus inhibits proliferation and migration, and induces apoptosis in hepatoma cells. The deregulation of AFP by HBP1 contributes to hepatoma progression in mice. Conclusion: Our data clarify the mechanism of HBP1 in inhibiting the expression of AFP and its suppression in malignancy of hepatoma cells, providing a more comprehensive theoretical basis and potential solutions for the early diagnosis and treatment of hepatoma.

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