• Title/Summary/Keyword: mi transcription factor

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Perilla Leaf Extract Inhibits 3T3-L1 Preadipocytes Differentiation

  • Kim, Mi-Ja;Kim, Hye-Kyung
    • Food Science and Biotechnology
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    • v.18 no.4
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    • pp.928-931
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    • 2009
  • Effects of perilla leaf extracts (PLE) on adipocytes differentiation of 3T3-L1 cells were examined. Ethanol extract of PLE treatment significantly decreased lipid accumulation, a marker of adipogenesis, in a dose-dependent manner. Moreover, gene expression levels of peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), the key adipogenic transcription factor, were markedly decreased by PLE. PLE also suppressed adipocyte fatty acid binding protein (aP2) and glycerol-3-phosphate dehydrogenase (GPDH), which are adipogenic marker proteins. These results suggest that PLE treatment suppressed differentiation of 3T3-L1 adipocytes, in part by down-regulating expression of adipogenic transcription factor and other specific target genes.

Signal Transducer and Activator of Transcription 3 - A Promising Target in Colitis-Associated Cancer

  • Pandurangan, Ashok Kumar;Esa, Norhaizan Mohd
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.2
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    • pp.551-560
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    • 2014
  • Colorectal cancer (CRC) is the third most common malignancy and fourth most common cause of cancer mortality worldwide. Untreated chronic inflammation in the intestine ranks among the top three high-risk conditions for colitis-associated colorectal cancer (CAC). Signal Transducer and Activator of Transcription 3 (STAT3) protein is a member of the STAT family of transcription factors often deregulated in CRC. In this review, we try to emphasize the critical role of STAT3 in CAC as well as the crosstalk of STAT3 with inflammatory cytokines, nuclear factor (NF)-${\kappa}B$, PI3K/Akt, Mammalian Target of Rapamycin (mTOR), Notch, $Wnt/{\beta}$-catenin and microRNA (MiR) pathways. STAT3 is considered as a primary drug target to treat CAC in humans and rodents. Also we updated the findings for inhibitors of STAT3 with regard to effects on tumorigenesis. This review will hopefully provide insights on the use of STAT3 as a therapeutic target in CAC.

Sinensetin Inhibits Interleukin-6 in Human Mast Cell - 1 Via Signal Transducers and Activators of the Transcription 3 (STAT3) and Nuclear Factor Kappa B (NF-κB) Pathways

  • Chae, Hee-Sung;Kim, Young-Mi;Chin, Young-Won
    • Natural Product Sciences
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    • v.23 no.1
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    • pp.1-4
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    • 2017
  • Sinensetin, a pentamethoxyflavone, is known to exert various pharmacological activities including anti-angiogenesis, anti-diabetic and anti-inflammatory activities. However, its effects on the human mast cell - 1 (HMC-1) mediated inflammatory mechanism remain unknown. To explore the mediator and cellular inflammatory response of sinensetin, we examined its influence on phorbol 12-myristate 13-acetate (PMA) plus A23187 induced inflammatory mediator production in a human mast cell line. In this study, interleukin (IL)-6 production was measured using the enzyme-linked immunosorbent assay and reverse transcription polymerase chain reaction. Sinensetin inhibited PMA plus A23187 induced IL-6 production in a dose-dependent manner as well as IL-4, IL-5 and IL-8 mRNA expression. Furthermore, sinensetin inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation, suggesting that sinensetin inhibits the production of inflammatory mediators by blocking STAT3 phosphorylation. Moreover, sinensetin was found to inhibit nuclear factor kappa B activation. These findings suggest that sinensetin may be involved in the regulation of mast cell-mediated inflammatory responses.

Understanding of the functional role(s) of the Activating Transcription Factor 4(ATF4) in HIV regulation and production

  • Lee, Seong-Deok;Yu, Kyung-Lee;Park, Seong-Hyun;Jung, Yu-Mi;Kim, Min-Jeong;You, Ji-Chang
    • BMB Reports
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    • v.51 no.8
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    • pp.388-393
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    • 2018
  • The activating transcription factor (ATF) 4 belongs to the ATF/CREB (cAMP Response Element Binding bZIP [Basic Leucine Zipper]) transcription factor family, and plays a central role in the UPR (Unfolded Protein Response) process in cells. The induction of ATF4 expression has previously been shown to increase the replication of HIV-1. However, the detailed mechanism underlying this effect and the factors involved in the regulation of ATF4 function are still unknown. Here, we demonstrate first that knocking out ATF4 using siRNA shows a strong negative effect on HIV-1 production, indicating that ATF4 is a functional positive cellular factor in HIV-1 production. To determine the mechanism by which ATF4 regulates the HIV-1 life cycle, we assessed the effect of the overexpression of wild type ATF4 and its various derivatives on HIV-1 LTR-mediated transcriptional activation and the production of HIV-1 particles. This effect was studied through co-transfection experiments with either reporter vectors or proviral DNA. We found that the N-terminal domains of ATF4 are involved in HIV-1 LTR-mediated transcriptional activation, and thus in HIV-1 production.

Cross-talk between Phosphate Starvation and Other Environmental Stress Signaling Pathways in Plants

  • Baek, Dongwon;Chun, Hyun Jin;Yun, Dae-Jin;Kim, Min Chul
    • Molecules and Cells
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    • v.40 no.10
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    • pp.697-705
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    • 2017
  • The maintenance of inorganic phosphate (Pi) homeostasis is essential for plant growth and yield. Plants have evolved strategies to cope with Pi starvation at the transcriptional, post-transcriptional, and post-translational levels, which maximizes its availability. Many transcription factors, miRNAs, and transporters participate in the Pi starvation signaling pathway where their activities are modulated by sugar and phytohormone signaling. Environmental stresses significantly affect the uptake and utilization of nutrients by plants, but their effects on the Pi starvation response remain unclear. Recently, we reported that Pi starvation signaling is affected by abiotic stresses such as salt, abscisic acid, and drought. In this review, we identified transcription factors, such as MYB, WRKY, and zinc finger transcription factors with functions in Pi starvation and other environmental stress signaling. In silico analysis of the promoter regions of Pi starvation-responsive genes, including phosphate transporters, microRNAs, and phosphate starvation-induced genes, suggest that their expression may be regulated by other environmental stresses, such as hormones, drought, cold, heat, and pathogens as well as by Pi starvation. Thus, we suggest the possibility of cross-talk between Pi starvation signaling and other environmental stress signaling pathways.

Mitochondria Control Protein as a Novel Therapeutic Target for Metabolic Syndrome

  • KimPak, Young-Mi
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2008.04a
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    • pp.23-30
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    • 2008
  • Mitochondria biogenesis requires a coordination of two genomes, nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). Disruption of mitochondria function leads to a loss of mitochondrial membrane potential and ATP generating capacity and consequently results in chronic degenerative diseases including insulin resistance, metabolic syndrome and neurodegenerative diseases. Although PPAR-${\gamma}$ coactivator-$1{\alpha}$ (PGC-$1{\alpha}$) was discovered as a central regulator of mitochondria biogenesis and a transcriptional co-activator of nuclear respiratory factor (NRF) and mitochondrial transcription factor A (Tfam), the expressions of PGC-$1{\alpha}$, NRF and Tfam were not significantly altered in tissues showing abnormal mitochondria functions. This observation suggests that there should be another regulator(s) for mitochondria function. Here, we demonstrate microRNAs (miRNAs) can modulate mitochondria function. Overexpression of microRNA dissipated mitochondrial membrane potential and increased ROS production in vitro and in vivo. It will be discussed the target of microRNA and its role in metabolic syndrome.

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Hypoosmotic shock adaptation by prolactin involves upregulation of arginine vasotocin and osmotic stress transcription factor 1 mRNA in the cinnamon clownfish Amphiprion melanopus

  • Park, Mi Seon;Kim, Na Na;Shin, Hyun Suk;Min, Byung Hwa;Kil, Gyung-Suk;Cho, Sung Hwoan;Choi, Cheol Young
    • Animal cells and systems
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    • v.16 no.5
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    • pp.391-399
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    • 2012
  • We cloned cDNA-encoding arginine vasotocin (AVT) from the brain of the cinnamon clownfish Amphiprion melanopus, and that was predicted to encode a protein of 153 amino acids. We examined changes in the expression of AVT mRNA in the brain and arginine vasotocin receptor (AVTR) mRNA and osmotic stress transcription factor 1 (OSTF1) mRNA in the gills of the cinnamon clownfish using quantitative real-time PCR in an osmotically changing environment (seawater (35 psu) ${\rightarrow}$ brackish water (BW, 17.5 psu) and BW with prolactin [PRL]). The expression of AVT, AVTR, and OSTF1 mRNA in the brain and gills increased after transfer to BW, and the expression was repressed by PRL treatment. AVT-immunoreactive cells were almost consistently observed in the telencephalon. The plasma $Na^+$ and $Cl^-$ levels decreased in BW, but the level of this parameter increased in BW with PRL treatme during salinity change. These results suggest that AVT, AVTR, and OSTF1 play important roles in hormonal regulation in osmoregulation organs, and that PRL improves the hyperosmoregulatory ability of cinnamon clownfish in BW environment.

Anti-Cancer Activity of the Flower Bud of Sophora japonica L. through Upregulating Activating Transcription Factor 3 in Human Colorectal Cancer Cells

  • Lee, Jin Wook;Park, Gwang Hun;Eo, Hyun Ji;Song, Hun Min;Kim, Mi Kyoung;Kwon, Min Ji;Koo, Jin Suk;Lee, Jeong Rak;Lee, Man Hyo;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.28 no.3
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    • pp.297-304
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    • 2015
  • The flower buds of Sophora japonica L (SF), as a well-known traditional Chinese medicinal herb, have been used to treat bleeding-related disorders such as hematochezia, hemorrhoidal bleeding, dysfunctional uterine bleeding, and diarrhea. However, no specific anti-cancer effect and its molecular mechanism of SF have been described. Thus, we performed in vitro study to investigate if treatment of SF affects activating transcription factor 3 (ATF3) expression and ATF3-mediated apoptosis in human colorectal cancer cells. The effects of SF on cell viability and apoptosis were measured by MTT assay and Western blot analysis against cleaved poly (ADP-ribose) polymerase (PARP). ATF3 activation induced by SF was evaluated using Western blot analysis, RT-PCR and ATF3 promoter assay. SF treatment caused decrease of cell viability and increase of apoptosis in a dose-dependent manner in HCT116 and SW480 cells. Exposure of SF activated the levels of ATF3 protein and mRNA via transcriptional regulation in HCT116 and SW480 cells. Inhibition of extracellular signal-regulated kinases (ERK) 1/2 by PD98059 and p38 by SB203580 attenuated SF-induced ATF3 expression and transcriptional activation. Ectopic ATF3 overexpression accelerated SF-induced cleavage of PARP. These findings suggest that SF-mediated apoptosis may be the result of ATF3 expression through ERK1/2 and p38-mediated transcriptional activation.

Screening of Transcriptional Regulator of the Draf Proto-oncogene Using the Yeast One-hybrid System

  • Park, So-Young;Park, Na-Hyun;Kwon, Eun-Jeong;Yoo, Mi-Ye
    • Journal of Life Science
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    • v.9 no.2
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    • pp.52-56
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    • 1999
  • The Raf, a cytoplasmic serine/thereonine protein kinase, acts as an important mediator of signals involving cell proliferation, differentiation and development. Multiple regulatory elements should participate in the expression of D-raf, Drosophila homolog of human c-raf-1. In order to search regulatory factors involved in the D-raf promoter activation, we accomplished the yeast one-hybrid screening using D-raf promoter region from bp-330 to -309 with respect to the transcription initiation site as bait. After screening, sixteen independent positive clones of ${\beta}$-galactosidase activties were identified and sequenced. Two clones having 94-98% identity with daughterless and one clone having 93% identity with escargot by Blast search among these clones were screened.