• Title/Summary/Keyword: transcription activity

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Phenolic Constituents with Inhibitory Activity against NFAT Transcription from Desmos chinensis

  • Kiem Phan Van;Minh Chau Van;Huang Hoang Thanh;Lee Jung Joon;Lee Im Seon;Kim Young Ho
    • Archives of Pharmacal Research
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    • v.28 no.12
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    • pp.1345-1349
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    • 2005
  • Six phenolic constituents, 2-methoxybenzyl benzoate (1), negletein (2), 2',3'-dihydroxy-4',6'­dimethoxydihydrochalcone (3), 5,6-dihydroxy-7-methoxy-dihydroflavone (4), astilbin (5), and quercitrin (6) were isolated from the methanol extract of the dried leaves of Desmos chinensis. Their structures were elucidated from spectral and chemical data. Of these constituents, compounds 2 ($IC_{50}$: 3.89 $\pm$ 0.39 $\mu$M) and 3 ($IC_{50}$: 9.77 $\pm$ 0.26 $\mu$M) exhibited potent inhibitory activity against nuclear factor of activated T cells (NFAT) transcription factor, and compound 1 ($IC_{50}$: 28.4 $\pm$ 2.62 $\mu$M) exhibited moderate inhibitory activity.

Diarylpropionitrile inhibits melanogenesis via protein kinase A/cAMP-response element-binding protein/microphthalmiaassociated transcription factor signaling pathway in α-MSH-stimulated B16F10 melanoma cells

  • Lee, Hyun Jeong;An, Sungkwan;Bae, Seunghee;Lee, Jae Ho
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.2
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    • pp.113-123
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    • 2022
  • Diarylpropionitrile (DPN), a selective agonist for estrogen receptor β (ERβ), has been reported to regulate various hormonal responses through activation of ERβ in tissues including the mammary gland and brain. However, the effect of DPN on melanogenesis independent of ERβ has not been studied. The aim of this study is to examine the possibility of anti-melanogenic effect of DPN and its underlying mechanism. Melanin contents and cellular tyrosinase activity assay indicated that DPN inhibited melanin biosynthesis in alpha-melanocyte stimulating hormone-stimulated B16F10 melanoma cell line. However, DPN had no direct influence on in vitro tyrosinase catalytic activity. On the other hand, 17β-estradiol had no effect on inhibition of melanogenesis, suggesting that the DPN-mediated suppression of melanin production was not related with estrogen signaling pathway. Immunoblotting analysis showed that DPN down-regulated the expression of microphthalmia-associated transcription factor (MITF), a central transcription factor of melanogenesis and its down-stream genes including tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. Also, DPN attenuated the phosphorylation of protein kinase A (PKA) and cAMP-response element-binding protein (CREB). Additionally, DPN suppressed the melanin synthesis in UVB-irradiated HaCaT conditioned media culture system suggesting that DPN has potential as an anti-melanogenic activity in physiological conditions. Collectively, our data show that DPN inhibits melanogenesis via downregulation of PKA/CREB/MITF signaling pathway.

Temporal Regulation of Ovine Interferon-tau Gene by the Transcription Factor Eomesodermin in the Peri-Implantation Period

  • Kim, Min-Su;Lim, Hyun-Joo;Lee, Ji Hwan;Hur, Tae Young;Son, Jun Kyu
    • Journal of Animal Reproduction and Biotechnology
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    • v.34 no.4
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    • pp.292-299
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    • 2019
  • Interferon tau (IFNT) regulation, an anti-luteolytic factor produced by conceptuses of the ruminant ungulates, is essential for the maintenance of early pregnancy, but a definitive mechanism for its temporal transcription has not been elucidated. We and others have observed the T-box protein eomesodermin (EOMES) exhibited high mRNA expression in the ovine embryonic trophectoderm; thus, both caudal-relatedhomeobox-2 (CDX2) and EOMES coexist during the early stages of conceptus development. Objective of this study was to examine the effect of EOMES on ovine IFNT gene transcription when evaluated with CDX2, ETS2 and AP1 transcription factors implicated in the control of cell differentiation in the trophectoderm. In this study, quantitatively via reverse transcription-polymerase chain reaction (RT-PCR) analysis between ovine trophoblast cells was initially performed, finding that transcription factors CDX2 and 'EOMES transcription factor mRNAs' were specific to trophectoderm cells. These mRNAs were also found in days 15, 17, and 21 ovine conceptuses. Furthermore, human choriocarcinoma JEG3 cells (trophoblast cell line) were cotransfected with an ovine IFNT (-654bp)-luciferase reporter (-654-oIFNT-Luc) construct and several transcription factor expression plasmids. Cotransfection of the reporter construct with CDX2, ETS2 and AP1 increased transcription of -654-oIFNT-Luc by about 11-fold compared with transfection of the construct alone. When cells were initially transfected with EOMES followed by transfection with CDX2, ETS2 and/or AP1, the expression of -654-oIFNT-Luc was decreased. Also, EOMES factor inhibited the stimulatory activity of CDX2 alone. These results suggest that when conceptuses attach to the uterine epithelium, ovine IFNT gene transcription is down-regulated by an increase of EOMES factor expression in the attached ovine trophoblast cells.

Effect of Yukmigihwang-tang kamibang on the Expression of Osteo-related Genes, TG2 and BMP4 (육미지황탕가미방이 골형성 관련 유전자인 TG2와 BMP4의 전사활성에 미치는 영향)

  • 신용욱;박용일;김홍렬;이응세
    • The Journal of Korean Medicine
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    • v.23 no.2
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    • pp.190-197
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    • 2002
  • Objectives : This study was performed to examine the effect of Yukmigiwhang-tang kamibang, a mixture of oriental herbal extracts, on the transcription of bone fonnation genes, BMP4 (bone morphogenetic protein 4) and TG2 (transglutaminase-2). Methods : Bone-related cells, MG-63 (human male osteosarcoma), HOS-TE85 (human female osteosarcoma), and KG-l (bone marrow) were cultured with portions of Yukmigiwhang-tang kamibang and the transcription activities of bone-related genes, BMP4 (bone morphogenetic protein 4) and TG2 (transglutaminase-2), were determined by Reverse-Transcription Polymerase Chain Reaction (RT-PCR). Results : Transcription of BMP4 gene in HOS-TE85 cell increased up to 40% at 0.3% (v/v) of Yukmigiwhang- tang kamibang extract and that of TG2 gene in MG-63 cells also increased up to 40% at 0.3-0.4% of the same extract. Although it was less significant when compared to those in other cells, the transcription of BMP4 gene in KG-l cells also increased up to 10 to 25%. Conclusions : These results clearly demonstrated that Yukmigiwhang-tang kamibang have an effect on transcription activity of bone-related genes, TG2 and BMP4, suggesting that it may play an important role in bone formation.

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Characterization of the Nanog 5'-flanking Region in Bovine

  • Choi, Don-Ho;Kim, Duk-Jung;Song, Ki-Duk;Park, Hwan-Hee;Ko, Tae Hyun;Pyao, Yuliya;Chung, Ku-Min;Cha, Seok Ho;Sin, Young-Su;Kim, Nam-Hyung;Lee, Woon-Kyu
    • Asian-Australasian Journal of Animal Sciences
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    • v.29 no.10
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    • pp.1383-1391
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    • 2016
  • Bovine embryonic stem cells have potential for use in research, such as transgenic cattle generation and the study of developmental gene regulation. The Nanog may play a critical role in maintenance of the undifferentiated state of embryonic stem cells in the bovine, as in murine and human. Nevertheless, efforts to study the bovine Nanog for pluripotency-maintaining factors have been insufficient. In this study, in order to understand the mechanisms of transcriptional regulation of the bovine Nanog, the 5'-flanking region of the Nanog was isolated from ear cells of Hanwoo. Results of transient transfection using a luciferase reporter gene under the control of serially deleted 5'-flanking sequences revealed that the -134 to -19 region contained the positive regulatory sequences for the transcription of the bovine Nanog. Results from mutagenesis studies demonstrated that the Sp1-binding site that is located in the proximal promoter region plays an important role in transcriptional activity of the bovine Nanog promoter. The electrophoretic mobility shift assay with the Sp1 specific antibody confirmed the specific binding of Sp1 transcription factor to this site. In addition, significant inhibition of Nanog promoter activity by the Sp1 mutant was observed in murine embryonic stem cells. Furthermore, chromatin-immunoprecipitation assay with the Sp1 specific antibody confirmed the specific binding of Sp1 transcription factor to this site. These results suggest that Sp1 is an essential regulatory factor for bovine Nanog transcriptional activity.

Regulation of signal transducer and activator of transcription 3 activation by dual-specificity phosphatase 3

  • Kim, Ba Reum;Ha, Jain;Kang, Eunjeong;Cho, Sayeon
    • BMB Reports
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    • v.53 no.6
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    • pp.335-340
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    • 2020
  • Since cancer is the leading cause of death worldwide, there is an urgent need to understand the mechanisms underlying cancer progression and the development of cancer inhibitors. Signal transducer and activator of transcription 3 (STAT3) is a major transcription factor that regulates the proliferation and survival of various cancer cells. Here, dual-specificity phosphatase 3 (DUSP3) was identified as a regulator of STAT3 based on an interaction screening performed using the protein tyrosine phosphatase library. DUSP3 interacted with the C-terminal domain of STAT3 and dephosphorylated p-Y705 of STAT3. In vitro dephosphorylation assay revealed that DUSP3 directly dephosphorylated p-STAT3. The suppressive effects of DUSP3 on STAT3 were evaluated by a decreased STAT3-specific promoter activity, which in turn reduced the expression of the downstream target genes of STAT3. In summary, DUSP3 downregulated the transcriptional activity of STAT3 via dephosphorylation at Y705 and also suppressed the migratory activity of cancer cells. This study demonstrated that DUSP3 inhibits interleukin 6 (IL-6)/STAT3 signaling and is expected to regulate cancer development. Novel functions of DUSP3 discovered in IL-6/STAT3 signaling regulation would help expand the understanding of cancer development mechanisms.

Autophagy and Longevity

  • Nakamura, Shuhei;Yoshimori, Tamotsu
    • Molecules and Cells
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    • v.41 no.1
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    • pp.65-72
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    • 2018
  • Autophagy is an evolutionally conserved cytoplasmic degradation system in which varieties of materials are sequestered by a double membrane structure, autophagosome, and delivered to the lysosomes for the degradation. Due to the wide varieties of targets, autophagic activity is essential for cellular homeostasis. Recent genetic evidence indicates that autophagy has a crucial role in the regulation of animal lifespan. Basal level of autophagic activity is elevated in many longevity paradigms and the activity is required for lifespan extension. In most cases, genes involved in autophagy and lysosomal function are induced by several transcription factors including HLH-30/TFEB, PHA-4/FOXA and MML-1/Mondo in long-lived animals. Pharmacological treatments have been shown to extend lifespan through activation of autophagy, indicating autophagy could be a potential and promising target to modulate animal lifespan. Here we summarize recent progress regarding the role of autophagy in lifespan regulation.

Histone H4-Specific Deacetylation at Active Coding Regions by Hda1C

  • Lee, Min Kyung;Kim, TaeSoo
    • Molecules and Cells
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    • v.43 no.10
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    • pp.841-847
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    • 2020
  • Histone acetylation and deacetylation play central roles in the regulation of chromatin structure and transcription by RNA polymerase II (RNA Pol II). Although Hda1 histone deacetylase complex (Hda1C) is known to selectively deacetylate histone H3 and H2B to repress transcription, previous studies have suggested its potential roles in histone H4 deacetylation. Recently, we have shown that Hda1C has two distinct functions in histone deacetylation and transcription. Histone H4-specific deacetylation at highly transcribed genes negatively regulates RNA Pol II elongation and H3 deacetylation at inactive genes fine-tunes the kinetics of gene induction upon environmental changes. Here, we review the recent understandings of transcriptional regulation via histone deacetylation by Hda1C. In addition, we discuss the potential mechanisms for histone substrate switching by Hda1C, depending on transcriptional frequency and activity.

Sarsasapogenin Increases Melanin Synthesis via Induction of Tyrosinase and Microphthalmia-Associated Transcription Factor Expression in Melan-a Cells

  • Moon, Eun-Jung;Kim, Ae-Jung;Kim, Sun-Yeou
    • Biomolecules & Therapeutics
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    • v.20 no.3
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    • pp.340-345
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    • 2012
  • Sarsasapogenin (SAR) is a steroidal sapogenin that is used as starting material for the industrial synthesis of steroids. It has various pharmacological benefits, such as antitumor and antidepressant activities. Since its effect on melanin biosynthesis has not been reported, we used murine melanocyte melan-a cells to investigate whether SAR influences melanogenesis. In this study, SAR significantly increased the melanin content of the melan-a cells from 1 to 10 ${\mu}M$. Based on an enzymatic activity assay using melan-a cell lysate, SAR had no effect on tyrosinase and DOPAchrome tautomerase activities. It also did not affect the protein expression of tyrosinase-related protein 1 and DOPAchrome tautomerase. However, protein levels of tyrosinase and microphthalmia-associated transcription factor were strongly stimulated by treatment with SAR. Therefore, our reports suggest that SAR treatment may induce melanogenesis through the stimulation of tyrosinase and microphthalmia-associated transcription factor expression in melan-a cells.

Presence of Transcription Factor OCT4 Limits Interferon-tau Expression during the Pre-attachment Period in Sheep

  • Kim, Min-Su;Sakurai, Toshihiro;Bai, Hanako;Bai, Rulan;Sato, Daisuke;Nagaoka, Kentaro;Chang, Kyu-Tae;Godkin, James D.;Min, Kwan-Sik;Imakawa, Kazuhiko
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.5
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    • pp.638-645
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    • 2013
  • Interferon-tau (IFNT) is thought to be the conceptus protein that signals maternal recognition of pregnancy in ruminants. We and others have observed that OCT4 expression persists in the trophectoderm of ruminants; thus, both CDX2 and OCT4 coexist during the early stages of conceptus development. The aim of this study was to examine the effect of CDX2 and OCT4 on IFNT gene transcription when evaluated with other transcription factors. Human choriocarcinoma JEG-3 cells were cotransfected with an ovine IFNT (-654-bp)-luciferase reporter (-654-IFNT-Luc) construct and several transcription factor expression plasmids. Cotransfection of the reporter construct with Cdx2, Ets2 and Jun increased transcription of -654-IFNT-Luc by about 12-fold compared with transfection of the construct alone. When cells were initially transfected with Oct4 (0 h) followed by transfection with Cdx2, Ets2 and/or Jun 24 h later, the expression of -654-IFNT-Luc was reduced to control levels. OCT4 also inhibited the stimulatory activity of CDX2 alone, but not when CDX2 was combined with JUN and/or ETS2. Thus, when combined with the other transcription factors, OCT4 exhibited little inhibitory activity towards CDX2. An inhibitor of the transcriptional coactivator CREB binding protein (CREBBP), 12S E1A, reduced CDX2/ETS2/JUN stimulated -654-IFNT-Luc expression by about 40%, indicating that the formation of an appropriate transcription factor complex is required for maximum expression. In conclusion, the presence of OCT4 may initially minimize IFNT expression; however, as elongation proceeds, the increasing expression of CDX2 and formation of the transcription complex leads to greatly increased IFNT expression, resulting in pregnancy establishment in ruminants.