scholarly journals Structure of theEscherichia coliAntitoxin MqsA (YgiT/b3021) Bound to Its Gene Promoter Reveals Extensive Domain Rearrangements and the Specificity of Transcriptional Regulation

2010 ◽  
Vol 286 (3) ◽  
pp. 2285-2296 ◽  
Author(s):  
Breann L. Brown ◽  
Thomas K. Wood ◽  
Wolfgang Peti ◽  
Rebecca Page
Author(s):  
Zhengyi Cao ◽  
Yuning Cheng ◽  
Jiyin Wang ◽  
Yujuan Liu ◽  
Ruixiang Yang ◽  
...  

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.


FEBS Letters ◽  
1999 ◽  
Vol 455 (1-2) ◽  
pp. 165-169 ◽  
Author(s):  
Hitomi Fukuda ◽  
Nobuko Iritani

1994 ◽  
Vol 14 (7) ◽  
pp. 4360-4372
Author(s):  
M E Carter ◽  
T Gulick ◽  
D D Moore ◽  
D P Kelly

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.


1993 ◽  
Vol 5 (5) ◽  
pp. 551-558 ◽  
Author(s):  
Euphemia Leung ◽  
Paul E. Mead ◽  
Qian Yuan ◽  
Wei-Meng Jiang ◽  
James D. Watson ◽  
...  

1994 ◽  
Vol 14 (7) ◽  
pp. 4360-4372 ◽  
Author(s):  
M E Carter ◽  
T Gulick ◽  
D D Moore ◽  
D P Kelly

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.


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