• Biomolecules & Therapeutics
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• 제22권4호
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• pp.308-313
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• 2014

Activator protein-1 (AP-1) is an inducible transcription factor that contributes to the generation of chronic inflammation in response to oxidative and electrophilic stress. Previous studies have demonstrated that the PI3K/Akt1 pathway plays an important role in the transcriptional regulation of AP-1 expression. Although the histone post-translational modifications (PTMs) are assumed to affect the AP-1 transcriptional regulation by the PI3K/Akt pathway, the detailed mechanisms are completely unknown. In the present study, we show that heterochromatin 1 gamma ($HP1{\gamma}$) plays a negative role in TPA-induced c-Jun and c-Fos expression. We show that TPA-induced Akt1 directly phosphorylates $HP1{\gamma}$, abrogates its suppressive function and increases the interaction between histone H3 and 14-3-$3{\varepsilon}$. Collectively, these our data illustrate that the activation of PI3K/Akt pathway may play a permissive role in the recruitment of histone readers or other coactivators on the chromatin, thereby affecting the degree of AP-1 transcription.

• BMB Reports
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• 제35권4호
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• pp.371-376
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• 2002

The receptor activator of nuclear factor kappa B (RANK) is a member of the tumor necrosis factor (TNF) receptor superfamily. It plays a critical role in osteoclast differentiaion, lymph node organogenesis, and mammary gland development. The stimulation of RANK causes the activation of transcription factors NF-${\kappa}B$ and activator protein 1 (AP1), and the mitogen activated protein kinase (MAPK) c-Jun N-terminal kinase (JNK). In the signal transduction of RANK, the recruitment of the adaptor molecules, TNF receptor-associated factors (TRAFs), is and initial cytoplasmic event. Recently, the association of the MAPK kinase kinase, transforming growth factor-$\beta$-activated kinase 1 (TAK1), with TRAF6 was shown to mediate the IL-1 signaling to NF-${\kappa}B$ and JNK. We investigated whether or not TAK1 plays a role in RANK signaling. A dominant-negative form of TAK1 was discovered to abolish the RANK-induced activation of AP1 and JNK. The AP1 activation by TRAF2, TRAF5, and TRAF6 was also greatly suppressed by the dominant-negative TAK1. the inhibitory effect of the TAK1 mutant on RANK-and TRAF-induced NF-${\kappa}B$ activation was also observed, but less efficiently. Our findings indicate that TAK1 is involved in the MAPK cascade and NF-${\kappa}B$ pathway that is activated by RANK.

• 한국임상수의학회지
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• 제32권4호
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• pp.289-294
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• 2015

Fucoidan은 갈조류로부터 추출되는 황산다당류로 다양한 생리학적 활성을 갖고 있다. 본 연구의 목적은 LPS로 자극한 돼지 말초혈액 단핵구세포(PBMCs)의 NO 생산에 있어 fucoidan의 효과를 검토하고, 이러한 효과가 iNOS의 발현과 AP-1의 활성화와 관련이 있는지를 조사하는데 있다. LPS 무처치 돼지 PBMCs에서 fucoidand의 처리는 NO 생산과 AP-1활성에 대해 효과를 보이지 않았다. 또한 iNOS와 AP-1의 mRNA 발현도 fucoidan 처치에 의해 영향을 받지 않았다. 그러나 LPS로 자극한 PBMCs에서는 NO 생산과 AP-1의 활성 그리고 iNOS와 AP-1의 mRNA 발현이 현저하게 증가하였다. 이와 같은 LPS에 의한 돼지 PBMCs의 NO 생산과 AP-1 활성증가는 fucoidan 첨가에 의해 감소되었다. 또한 fucoidan은 LPS에 의한 iNOS와 AP-1의 mRNA 발현증가도 억제시켰다. 이상의 결과는 fucoidan이 LPS 자극 돼지 PBMCs에서 iNOS 발현과 AP-1 활성의 억제와 함께 NO 생산을 하향 조절함으로써 항염증효과를 나타내는 것으로 사료되었다.

• 융합정보논문지
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• 제7권6호
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• pp.89-95
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• 2017

암을 유발하는 PMA는 세포를 자극하여 전사인자 C-Jun/C-fos의 발현을 증가시키며 핵 내의 AP-1의 활성을 증가하게 되고 결과적으로 각종 암이 발생된다고 보고되고 있다. 본 연구에서는 천연물 지표성분의 안전성을 보기위한 세포독성과 암예방 효과를 예측할 수 있는 Activator protein(AP-1) 활성억제를 관찰하였다. 천연물 지표성분 38종을 대상으로 세포독성과 AP-1 활성억제를 관찰한 결과 섬수의 지표성분인 Bufogein 과 Cinobufagin에서는 세포독성을 보이며 AP-1 활성 억제와 비교 시 5배 정도 차이를 보임을 알 수가 있다. 반면에 Arctigenin, Manassantin A, B에서는 AP-1 활성 억제 농도는 $2{\mu}M$ 이하이면서 세포독성과의 비율은 15배 이상임을 알 수 있다. 본 실험의 결과를 통해 우방자와 삼백초의 지표성분인 Arctigenin, Manassantin A,B는 암 예방 연구의 가능성을 시사하였다.

• BMB Reports
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• 제43권1호
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• pp.17-22
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• 2010

In this study, a novel member of BTB-kelch proteins, named KBTBD7, was cloned from a human embryonic heart cDNA library. The cDNA of KBTBD7 is 3,008 bp long and encodes a protein product of 684 amino acids (77.2 kD). This protein is highly conserved in evolution across different species. Western blot analysis indicates that a 77 kD protein specific for KBTBD7 is wildly expressed in all embryonic tissues examined. In COS-7 cells, KBTBD7 proteins are localized to the cytoplasm. KBTBD7 is a transcription activator when fused to GAL4 DNA-binding domain. Deletion analysis indicates that the BTB domain and kelch repeat motif are main regions for transcriptional activation. Overexpression of KBTBD7 in MCF-7 cells activates the transcriptional activities of activator protein-1 (AP-1) and serum response element (SRE), which can be relieved by siRNA. These results suggest that KBTBD7 proteins may act as a new transcriptional activator in mitogen-activated protein kinase (MAPK) signaling.

• BMB Reports
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• 제32권6호
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• pp.594-598
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• 1999

The Jun and Fos families of eukaryotic transcription factors form heterodimers capable of binding to their cognate DNA enhancer elements. We are interested in searching for inhibitors or antagonists of the binding of the Jun-Fos heterodimer to the activator protein-1 (AP-1) site. The basic-region leucine zipper (bZIP) domain of c-Fos was expressed as a fusion protein with glutathione S-transferase, and allowed to form a heterodimer with the bZIP domain of c-Jun. The heterodimer was bound to glutathione-agarose, to which were added radiolabeled AP-1 nucleotides. After thorough washing, the gel-bound radioactivity was counted. The assay is faster than the coventional electrophoretic mobility shift assay because the gel electrophoresis step and the autoradiography step are eliminated. Moreover, the assay is very sensitive, allowing the detection of picomolar quantities of nucleotides, and is not affected by up to 50% dimethylsulfoxide, a solvent for hydrophobic inhibitors. Curcumin and dihydroguaiaretic acid, recently known inhibitors of Jun-Fos-DNA complex formation, were applied to this Jun-GST-fused Fos system and revealed to decrease the dimer-DNA binding.

• BMB Reports
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• 제36권1호
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• pp.66-77
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• 2003

Tea is one of the most popular beverages consumed in the world and has been demonstrated to have anti-cancer activity in animal models. Research findings suggest that the polyphenolic compounds, (-)-epigallocatechin-3-gallate, found primarily in green tea, and theaflavin-3,3'-digallate, a major component of black tea, are the two most effective anti-cancer factors found in tea. Several mechanisms to explain the chemopreventive effects of tea have been presented but others and we suggest that tea components target specific cell-signaling pathways responsible for regulating cellular proliferation or apoptosis. These pathways include signal transduction pathways leading to activator protein-1 (AP-1) and/or nuclear factor kappa B(NF-${\kappa}B$ ). AP-1 and NF-${\kappa}B$ are transcription factors that are known to be extremely important in tumor promoter-induced cell transformation and tumor promotion, and both are influenced differentially by the MAP kinase pathways. The purpose of this brief review is to present recent research data from other and our laboratory focusing on the tea-induced cellular signal transduction events associated with the MAP kinase, AP-1, and NF-${\kappa}B$ pathways.

• BMB Reports
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• 제42권11호
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• pp.758-763
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• 2009

Cancer-associated antigen (CAGE) induces the expression of matrix metalloproteinase-2 (MMP-2) by activating Akt, which in turn interacts with inhibitory kappa kinase $\beta$ ($I{\kappa}K{\beta}$) to activate nuclear factor ${\kappa}B$ (NF-${\kappa}B$). Akt and p38 mitogen activated protein kinase (p38 MAPK) are necessary for CAGE-mediated induction of the AP-1 subunit JunB, whereas extracellular regulated kinase (ERK) is necessary for the induction of fos-related antigen-1 (Fra-1). Induction of MMP-2 by CAGE requires activator of protein-1 (AP-1) to be bound. Specific binding of JunB to MMP-2 promoter sequences was shown by chromatin immunoprecipitation (ChIP) analysis.

• 대한통합의학회지
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• 제12권1호
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• pp.63-71
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• 2024

Purpose : Skin is the primary barrier to protect the body from various exogenous factors. Among them, UVB exposure can cause the induction of not only excessive inflammatory responses but also the degradation of extracellular matrix (ECM), including collagen and elastin. This study tried to investigate the ameliorative effect of Persicaria perfoliata ethanol extract (PPEE) on UVB-irradiated photodamage through the regulation of activator protein (AP)-1, phosphoinositide 3-kinase (PI3K)/Akt, and mitogen-activated protein kinase (MAPK) signaling molecules in HaCaT cells. Methods : The cytotoxicity of PPEE on HaCaT cells was evaluated by the WST-1 assay. The 80 mJ/cm² of UVB (312 nm) was irradiated on HaCaT cells to induce the photodamage. Western blot analysis was conducted to investigate the protein expression levels of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9, and heme oxygenase (HO)-1 for ameliorative status by PPEE treatment in UVB-exposed HaCaT cells. In addition, the activated status of the inflammatory transcription factor, AP-1, as well as upstream signaling molecules, PI3K/Akt, and MAPK, were also evaluated by Western blot analysis. Results : Any cytotoxic effect was not induced at the concentration up to 200 ㎍/ml by PPEE treatment. Protein expression levels of COX-2 and MMP-9 were significantly down- and up-regulated by PPEE treatment. The inflammatory transcription factor AP-1, stimulated by UVB irradiation, was also significantly attenuated by PPEE treatment. The phosphorylated status of PI3K/Akt and MAPK were mitigated by PPEE treatment in UVB-exposed HaCaT cells. Moreover, PPEE treatment potently accelerated the expression of HO-1 and its transcription factor, nuclear factor-erythroid 2-related factor (Nrf)2, which is known for its anti-inflammatory activity. Conclusion : Consequently, PPEE treatment significantly regulated COX-2 and MMP-9 expressions in UVB-irradiated HaCaT cells. The inflammatory transcription factor AP-1, along with upstream signaling molecules PI3K/Akt and MAPKs, were also attenuated by PPEE treatment in UVB-exposed HaCaT cells. Additionally, PPEE treatment exaggerated HO-1 expression and Nrf2 activation, which might have contributed to the anti-inflammatory activity of PPEE. These results indicate that PPEE could be a candidate for attenuating UVB-induced photodamage in human skin.

• 한국가금학회:학술대회논문집
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• 한국가금학회 1999년도 제16차 정기총회및학술발표회
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• pp.34-50
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• 1999

A cDNA encoding chicken interferon-gamma (chIFN-${\gamma}$) was amplified from P34, a CD4$^{+}$ T-cell hybridoma by reverse transcription-polymerase chain reaction (RT-PCR) and cloned into pUC18. THe sequences of cloned PCR products were determined to confirm the correct cloning. Using this cDNA as probe, chicken genomic library from White Leghorn spleen was screened. Phage clones harboring chicken interferon-gamma (chIFN-${\gamma}$) were isolated and their genomic structure elucidated. The chIFN-${\gamma}$ contains 4 exons and 3 introns spanning over 14 kb, and follows the GT/AG rule for correct splicing at the exon/intron boundaries. The four exons encode 41, 26, 57 and 40 amino acids, respectively, suggesting that the overall structure of IFN-${\gamma}$ is evolutionairly conserved in mammalian and avian species. The 5’-untranslated region and signal sequences are located in exon 1. Several AT-rich sequences located in the fourth exon may indicate a role in mRNA turnover. The 5’-flanking region contains sequences homologous to the potential binding sites for the mammalian transcription factors, activator protein-1(AP-1) activator protein-2(AP-2) cAMP-response element binding protein(CREB), activating transcription factor(ATF), GATA-binding fator(GATA), upstream stimulating factor(USF), This suggests that the mechanisms underlying transcriptional regulation of chicken and mammalian IFN-${\gamma}$ genes may be similar.r.