• Biomolecules & Therapeutics
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• 제6권3호
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• pp.276-282
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• 1998

Retinoids regulate a wide variety of biological processes such as cellular proliferation and differentiation in many cell types. They have also shown to stimulate replication of several viruses including human cytomegalovirus (CMV). Retinoid signalling pathway involves two distinct subfamilies of nuclear receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs) that bind to specific retinoic acid response elements (RAREs) in the promoter regions of retinoid-target genes. Here, we characterized RAREs in the regulatory regions of the CMV and of the hepatitis B vi.us (HBV). The viral RAREs, i.e., CMV-RARE and HBV-RARE, are composed of two consensus RARE half-sites (A/GGGTCA) arranged as a direct repeat separated by 5-bp and 1-bp, respectively. The RAREs were activated by both RAR/RXR heterodimers and RXR homodimers in transient transfection experiments. We also found that COUP-TF$\alpha$ (chicken ovalbumin upstream promoter-transcription factor u) and COUP-TF$\beta$ repressed the retinoid response of the viral elements. Further we demonstrated that previously known retinoid antagonist, SRI 1330, repressed retinoid-induced transactivation of the CMV-RARE. These results implicate Vitamin A, it's nuclear receptors and COUP-TFs as important regulators of the CMV and HBV pathogenesis and the SRl1330 as potential negative modulator of such retinoid-dependent processes.

• 생명과학회지
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• 제15권2호
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• pp.186-191
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• 2005

Previous studies have demonstrated that expression of galectin-3, a member of family of beta-galactoside-binding animal lectin, is associated with pathological conditions including cancer, atherosclerosis, and viral infection. An increase of this lectin has been observed after infection by Kirsten murine sarcoma, human T lymphotropic virus-l (HTLV-l), and human immunodeficiency virus-l (HIV-l). Viral transactivation protein Tax of HTLV-l mediates the increase in the lectin. In case of HIV-1, there are evidences that Tat would be related with increase in galectin-3. We investigated whether Tat directly induced galectin-3 expression in cells. We found that HIV-l tat gene activated galectin-3 promoter in RAW264.7 cells. To demonstrate direct induction of galectin-3 by HIV-l tat, we transfected the tat into a rabbit smooth muscle cell line (Rb1) and obtained RblTatCl-2, a clone of cell stably transfected with tat gene. The Rb1TatCl-2 cells exhibited activation of LTR promoter and up-regulation of galectin-3 transcript as well as protein. Our results indicate that HIV-l tat alone is sufficient to induce the expression of galectin-3. The Rb1TatCl-2 cells could be valuable for study of the effect of HIV-1 tat on expression of cellular genes.

• Journal of Plant Biotechnology
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• 제39권3호
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• pp.175-181
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• 2012

Drought and high salinity stresses often imposes adverse effects on crop yield. MYB transcription factors have been shown to be an important regulator in defense responses to these environmental stresses. In this study, we have cloned and characterized a soybean gene GmMYB184 (Glycine max MYB transcription factor 184). Deduced amino acid sequences of GmMYB184 show highest homology with that from Vitis vinifera legume plant (75%). Different expression patterns of GmMYB184 mRNA were observed subjected to drought, cold, high salinity stress and abscisic acid treatment, suggesting its role in the signaling events in the osmotic stress-related defense response. Subcellular localization studies demonstrated that the GFP-GmMYB184 fusion protein was localized in the nucleus. Using the yeast assay system, the C-terminal region of GmMYB184 was found to be essential for the transactivation activity. These results indicate that the GmMYB184 may play a role in abiotic stress tolerance in plant.

• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.211-218
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• 2015

The present study showed that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibited lipopolysaccharide (LPS)-induced morphological changes in the mouse RAW264.7 macrophage cell line. We also showed that silymarin inhibited the nuclear translocation and transactivation activities of nuclear factor-kappa B (NF-${\kappa}B$), which is important for macrophage activation-associated changes in cell morphology and gene expression of inflammatory cytokines. BAY-11-7085, an NF-${\kappa}B$ inhibitor, abrogated LPS-induced morphological changes and NO production, similar to silymarin. Treatment of RAW264.7 cells with silymarin also inhibited LPS-stimulated activation of mitogen-activated protein kinases (MAPKs). Collectively, these experiments demonstrated that silymarin inhibited LPS-induced morphological changes in the RAW264.7 mouse macrophage cell line. Our findings indicated that the most likely mechanism underlying this biological effect involved inhibition of the MAPK pathway and NF-${\kappa}B$ activity. Inhibition of these activities by silymarin is a potentially useful strategy for the treatment of inflammation because of the critical roles played by MAPK and NF-${\kappa}B$ in mediating inflammatory responses in macrophages.

• The Korean Journal of Physiology and Pharmacology
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• 제12권5호
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• pp.281-286
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• 2008

Although the interaction between gp130 and the ErbB family has frequently been shown in cancer cells, the mechanism of this interaction remains unclear and controversial. In the present study, we found that specific tyrphostin inhibitors of ErbB2 (AG825 and AG879), but not ErbB1 inhibitor (AG1478), suppressed IL-6-induced tyrosine phosphorylation of STAT3 in schwannoma cells. However, biochemical evidence for transactivation of ErbB2 by IL-6 was not observed. Additionally, the inhibition of ErbB2 expression, with either a specific RNAi or transfection of an ErbB2 mutant lacking the intracellular domain did not inhibit the IL-6-induced tyrosine phosphorylation of STAT3. Thus, it seems that tyrphostins, which are known as specific inhibitors of the ErbB2 kinase, may have non-specific suppressive effects on the IL-6/STAT3 pathway.

• 한국자기공명학회논문지
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• 제9권2호
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• pp.122-137
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• 2005

The hepatitis B virus X protein (HBx) is highly linked with liver diseases and the development of hepatocellular carcinoma. HBx-interacting protein (XIP) has been shown to abolish the transactivation functions of HBx. Here, we define the structural characteristics and HBx binding properties of XIP. Under physiological conditions, XIP was composed mainly of random-coils but significant helicity was induced in the hydrophobic condition. NMR spectroscopy defined the secondary structure of XIP in the presence of sodium dodecyl sulfate. Four putative helices were mapped to the amino acids 8-12, 32-38, 42-54 and 82-91. Any deletion of defined putative helices in XIP led to loss of binding to HBx, and truncated mutant lacking last putative helix decreased helicity more than that it could. Our results suggest that XIP requires its entire sequence for HBx binding and it may be under drastic conformational change when binds to HBx.

• Animal cells and systems
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• 제4권4호
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• pp.389-394
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• 2000

The Tcf-1 (1-cell factor-1) protein binds to the T-cell specific enhancer sequences and plays an architectural role in the assembly of transcriptional machinery. One of the Tcf family proteins, Tcf-4, was found to be an important regulator for colon cancer development where it activates specific genes upon binding to $\beta$-catenin following Wnt signaling. We were interested in the transcriptional regulatory activities of Tcf-1 and Tcf-4 proteins in T-cells and colon cancer cells. Transactivation assay was developed using a reporter plasmid containing luciferase gene under the control of Tcf responsive elements. Luciferase activity was determined following co-transfection of the reporter along with Tcf-1 and/or $\beta$-catenin expressing plasmids. Transcription was significantly induced by $\beta$-catenin expression in all cells. Tcf-1 by itself did not induce transcription in the mature T-cell lines, but overexpressed Tcf-1 greatly activated transcription in the immature T-cell line. In addition, transfected $\beta$-catenin induced apoptosis, but co-transfected Tcf-1 suppressed apoptosis in HEK293 cells. These results suggest that Tcf-1 and $\beta$-catenin differently regulate transcription and apoptosis.

• BMB Reports
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• 제52권7호
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• pp.469-474
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• 2019

Kruppel-like factor 2 (KLF2) has been implicated in the regulation of cell proliferation, differentiation, and survival in a variety of cells. Recently, it has been reported that KLF2 regulates the p65-mediated transactivation of $NF-{\kappa}B$. Although the $NF-{\kappa}B$ pathway plays an important role in the differentiation of osteoclasts and osteoblasts, the role of KLF2 in these bone cells has not yet been fully elucidated. In this study, we demonstrated that KLF2 regulates osteoclast and osteoblast differentiation. The overexpression of KLF2 in osteoclast precursor cells inhibited osteoclast differentiation by downregulating c-Fos, NFATc1, and TRAP expression, while KLF2 overexpression in osteoblasts enhanced osteoblast differentiation and function by upregulating Runx2, ALP, and BSP expression. Conversely, the downregulation of KLF2 with KLF2-specific siRNA increased osteoclast differentiation and inhibited osteoblast differentiation. Moreover, the overexpression of interferon regulatory protein 2-binding protein 2 (IRF2BP2), a regulator of KLF2, suppressed osteoclast differentiation and enhanced osteoblast differentiation and function. These effects were reversed by downregulating KLF2. Collectively, our data provide new insights and evidence to suggest that the IRF2BP2/KLF2 axis mediates osteoclast and osteoblast differentiation, thereby affecting bone homeostasis.

• Biomolecules & Therapeutics
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• 제29권5호
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• pp.519-526
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• 2021

In a search for effective PPAR-γ agonists, 110 clinical drugs were screened via molecular docking, and 9 drugs, including parecoxib, were selected for subsequent biological evaluation. Molecular docking of parecoxib to the ligand-binding domain of PPAR-γ showed high binding affinity and relevant binding conformation compared with the PPAR-γ ligand/antidiabetic drug rosiglitazone. Per the docking result, parecoxib showed the best PPAR-γ transactivation in Ac2F rat liver cells. Further docking simulation and a luciferase assay suggested parecoxib would be a selective (and partial) PPAR-γ agonist. PPAR-γ activation by parecoxib induced adipocyte differentiation in 3T3-L1 murine preadipocytes. Parecoxib promoted adipogenesis in a dose-dependent manner and enhanced the expression of adipogenesis transcription factors PPAR-γ, C/EBPα, and C/EBPβ. These data indicated that parecoxib might be utilized as a partial PPAR-γ agonist for drug repositioning study.

• 대한한의학방제학회지
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• 제30권4호
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• pp.225-231
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• 2022

Objectives : Oxidative damage has a variety of mechanism in the human organs including brain and liver. The purpose of this study is to examine the prevention against cellular damage, and the inhibitory effect on lipogenesis of the water extract of Eriobotrya japonica (EJE). Methods : The effect of EJE on cell viability was assessed using the MTT assay. To investigate the mechanism of EJE's inhibition of lipogenesis, we analyzed the relevant proteins using immunoblot analysis. Results : Induction of T0901317, a LXR agonist, significantly increased SREBP-1c expression, which was blocked by the pretreatment of EJE in the dose-dependent manners. This beneficial herb also regulated the genes related with SREBP-1c such as the acetyl-CoA carboxylase. Conclusion : These results suggested that EJE might have a possibility of the treatment of chronic diseases as mediated with the inhibition of LXRα/SREBP-1c pathway.