• Title/Summary/Keyword: the transcription factors

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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.

Virus-induced Silencing of the WRKY1 Transcription Factor that Interacts with the SL1 Structure of Potato virus X Leads to Higher Viral RNA Accumulation and Severe Necrotic Symptoms

  • Park, Sang-Ho;Kim, Kook-Hyung
    • The Plant Pathology Journal
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    • v.28 no.1
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    • pp.40-48
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    • 2012
  • $Potato$ $virus$ $X$ (PVX) replication is precisely regulated by regulatory viral sequences and by viral and/or host proteins. In a previous study, we identified a 54-kDa cellular tobacco protein that bound to a region within the first 46 nucleotides (nt) of the 5' non-translated region (NTR) of the viral genome. Optimal binding was dependent upon the presence of an ACCA sequence at nt 10-13. To identify host factors that bind to 5' NTR elements including AC-rich sequences as well as stemloop 1 (SL1), we used northwestern blotting and matrixassisted laser desorption/ionization time-of-flight mass spectrometry for peptide mass fingerprinting. We screened several host factors that might affect PVX replication and selected a candidate protein, $Nicotiana$ $tabacum$ WRKY transcription factor 1 (NtWRKY1). We used a $Tobacco$ $rattle$ $virus$ (TRV)-based virus-induced gene silencing (VIGS) system to investigate the role of NtWRKY1 in PVX replication. Silencing of $WRKY1$ in $Nicotiana$ $benthamiana$ caused lethal apical necrosis and allowed an increase in PVX RNA accumulation. This result could reflect the balancing of PVX accumulation in a systemic $N.$ $benthamiana$ host to maintain PVX survival and still produce a suitable appearance of mosaic and mottle symptoms. Our results suggest that PVX may recruit the WRKY transcription factor, which binds to the 5' NTR of viral genomic RNA and acts as a key regulator of viral infection.

Suppressive effects of Morus alba Linne Root Bark (MRAL) on activation of MC/9 mast cells (상백피에 의한 MC/9 비만세포의 활성 억제 조절 연구)

  • Lee, Ki Jeon;Kim, Bok Kyu;Kil, Ki Jung
    • The Korea Journal of Herbology
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    • v.28 no.1
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    • pp.33-42
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    • 2013
  • Objective : Morus alba Linne Root Bark (MRAL) is a medicinal herb in Korean Medicine, known for its anti-inflammatory and anti-allergic properties. However, its mechanisms of action and the cellular targets have not yet been found and the study was developed to investigate the allergic suppressive effect of MRAL. The purpose of this study is to investigate the allergic suppressive effects of MRAL on activation of MC/9 mast cells. Methods : Cytotoxic activity of MRAL (50, 100, 200, 400 ${\mu}g/mL$) on MC/9 mast cells measured using EZ-Cytox cell viability assay kit (WST reagent). The levels of interleukin-5 (IL-5), IL-13 and IL-4, IL-5, IL-6, IL-13 mRNA expression were measured by enzyme-linked immunosorbent assay (ELISA) and real-time PCR respectively. The expression of transcription factors such as GATA-1, GATA-2, NFAT, AP-1 and NF-${\kappa}B$ p65 DNA binding activity were measured by western blot and electrophoresis mobility shift assay (EMSA). Results : Our results indicated that MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) significantly inhibited PMA/Ionomycin-induced production of IL-5 and IL-13 and the expression of IL-4, IL-5, IL-6 and IL-13 mRNA in MC/9 mast cells. Moreover, MRAL (50 ${\mu}g/mL$, 100 ${\mu}g/mL$) inhibited PMA/Ionomycin-induced GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos protein expression and NF-${\kappa}B$ p65 DNA binding activity in MC/9 mast cells. Conclusions : In conclusion, we suspect the anti-allergenic activities of MRAL, may be related to the regulation of transcription factors GATA-1, GATA-2, NFAT-1, NFAT-2, c-Fos and NF-${\kappa}B$ p65 DNA binding assay causing inhibition of Th2 cytokines IL-5 and IL-13 in mast cells.

Effect of Steroid Hormones on the Expression of c-Fos, CREB, ATF, and HSP70 in Rat Uterus (흰쥐 자궁에서 스테로이드호르몬에 의한 c-Fos, CREB, ATF 및 HSP70의 발현에 관한 연구)

  • Lee, Young-Ki;Kim, Sung-Rye
    • Clinical and Experimental Reproductive Medicine
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    • v.25 no.3
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    • pp.305-313
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    • 1998
  • Steroid hormone is known to cause the dynamic changes of mammalian uterus during reproductive cycle. However there is little information about the effect of estrogen (E) and progesterone (P) on the expression of various transcription factors involved in gene expression. Thus the present study was designed to demonstrate E and/or P-induced expression of c-Fos, CREB, ATF and HSP70 in rat uterus. Rats, ovariectomized (OVX) for two weeks, were divided into 6 experimental groups, 1) OVX, 2) OVX+V, 3) OVX+E, 4) OVX+P, 5) OVX+E+V, 6) OVX+E+P, and western blotting assay for nuclear extract and immunohistochemical staining were carried out for each experimental group. Treatment of E $(10{\mu}g)$ showed to increase the expression of c-Fos, CREB, ATF, and HSP70, and maximal expression was occured at $3\sim6$ hr after E administration. P (1mg) also increased, but much less than E, the expression of c-Fos, ATF, and HSP70. However, P did not reveal any effect on the expression CREE. P treatment 4 hr after E injection decreased c-Fos, CREB, and ATF expression, but did not show any change in the E-induced HSP70 expression. In immunohistochemical study c-Fos-, CREB-, and ATF-immunoreactivities were confined to the cells of luminal epithelium of uterine endometrium. These results suggest that proliferation and differentiation of rat uterus during reproductive cycle may mediated via expression of transcription factors, such as c-Fos, CREB, ATF, and HSP70.

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Post-Translational Regulations of Transcriptional Activity of RUNX2

  • Kim, Hyun-Jung;Kim, Woo-Jin;Ryoo, Hyun-Mo
    • Molecules and Cells
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    • v.43 no.2
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    • pp.160-167
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    • 2020
  • Runt-related transcription factor 2 (RUNX2) is a key transcription factor for bone formation and osteoblast differentiation. Various signaling pathways and mechanisms that regulate the expression and transcriptional activity of RUNX2 have been thoroughly investigated since the involvement of RUNX2 was first reported in bone formation. As the regulation of Runx2 expression by extracellular signals has recently been reviewed, this review focuses on the regulation of post-translational RUNX2 activity. Transcriptional activity of RUNX2 is regulated at the post-translational level by various enzymes including kinases, acetyl transferases, deacetylases, ubiquitin E3 ligases, and prolyl isomerases. We describe a sequential and linear causality between post-translational modifications of RUNX2 by these enzymes. RUNX2 is one of the most important osteogenic transcription factors; however, it is not a suitable drug target. Here, we suggest enzymes that directly regulate the stability and/or transcriptional activity of RUNX2 at a post-translational level as effective drug targets for treating bone diseases.

The Effects of Endurance Exercise and Selenium Treatment on Mitochondrial Transcription Factors Expression in Old GK Rats (지구성 운동과 셀레늄 투여가 노화 GK 흰쥐의 미토콘드리아 전사인자 발현에 미치는 영향)

  • Kim, Bum-Soo
    • Development and Reproduction
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    • v.14 no.2
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    • pp.75-82
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    • 2010
  • The objective of this study is to identify the effects of endurance exercise and selenium on mitochondrial transcription factor in old Goto-Kakizaki (GK) rats. In this experiments, endurance exercise were treadmill-run at 24 m/min, 30 min/day, 5 days/week, 6 weeks and 5 umol/kg of sodium selenite was injected intraperitoneally. In exercise group, selenium group, and combination group, the mitohondrial biogenesis-related genes, including PGC-$1{\alpha}$, NRF-1, and Tfam expression level were significantly increased compared to control group. Consistent with the increased biogenesis-related genes, the cytochrome C in the treated groups, which was the indicator of mitochondrial content, was significantly increased compared to control group. Especially, combination of exercise and selenium may be effective in the increase of mitochondrial biogenesis, activity and insulin sensitivity. Therefore, exercise and selenium treatment is likely to promote diabeticmitochondrial malfunction and then improve diabetes.

Overexpression of OsNAC17 enhances drought tolerance in rice

  • Kim, Tae Hwan;Kim, Ju-Kon
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.168-168
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    • 2017
  • Drought conditions during cultivation reduce agricultural production yield less than a theoretical maximum yield under normal condition. Plant specific NAC transcription factors in rice are known to play an essential roles in stress resistance transcriptional regulation. In this study, we report the rice (Oryza sativa L japonica) NAM, AFTF and CUC transcription factor OsNAC17, which is predominantly induced by abiotic stress in leaf, was contribute to the drought tolerance mediated reactive oxygen species (ROS) in transgenic rice plants. Constitutive (PGD1) promoter was introduced to overexpress OsNAC17 and produced the transgenic PDG1:OsNAC17. Overexpression of OsNAC17 throughout the whole plant improved drought resistance phenotype at the vegetative stage. Morphological characteristics such as grain yield, grain filling rate, and total grain weight improved by 22~64% over wild type plants under drought conditions during the reproductive stage. The improved drought tolerance in transgenic rice was involved in reducing stomatal density up to 15% than in wild type plants and in increasing reactive oxygen species-scavenging enzyme. DEG profiling experiment identified 119 up-regulated genes by more than twofold (P<0.01). These genes included UDP-glycosyltransferase family protein, similar to 2-alkenal reductase (NADPH-dependent oxireductase), similar to retinol dehydrogenase 12, Lipoxygenase, and NB-ARC domain containing protein related in cell death. Furthermore, OsNAC17 was act as a transcriptional activator, which has an activation domain in C-terminal region. These result demonstrate that the overexpression of OsNAC17 improve drought tolerance by regulating ROS scavenging enzymes and by reducing stomatal density

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Expression of ATE2 Transcription Factor and the Interaction with AP-1 Factors : BATF, c-Fos, c-Jun (ATF2 전사인자의 발현과 AP-1 전사인자인 BATF, c-Fos, c-Jun과의 이량체 형성)

  • Jang Hye-Young;Kim Jae-Ho
    • Journal of Life Science
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    • v.15 no.6 s.73
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    • pp.928-934
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    • 2005
  • ATF2 is a cellular transcription factor which belongs to the CREB/ATF class and it is leucine zipper protein which generally binds to DNA as dimers. This paper presents the procedure for subcloning the ATF2 gene and the results of experiment used the expressed ATF2. The pET expression vector was used since it produced 6xHis fusion protein for easy purification using affinity column. The Nickel chelating chromatography was used for Purifying the expressed ATE2 from E- codi BL2l. Subsequen시y In vitro binding pull-down assay showed the binding specificity of ATF2 with AP-1 family factors such as BATF, c-Fos, c-Jun and ATF2 itselgf. ATF2 forms homodimer as well as strong heterodimer with BATF. It also forms stable dimer with c-Jun but barely binds with c-Fos.

Roles of Forkhead-box Transcription Factors in Controlling Development, Pathogenicity, and Stress Response in Magnaporthe oryzae

  • Park, Jaejin;Kong, Sunghyung;Kim, Seryun;Kang, Seogchan;Lee, Yong-Hwan
    • The Plant Pathology Journal
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    • v.30 no.2
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    • pp.136-150
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    • 2014
  • Although multiple transcription factors (TFs) have been characterized via mutagenesis to understand their roles in controlling pathogenicity and infection-related development in Magnaporthe oryzae, the causal agent of rice blast, if and how forkhead-box (FOX) TFs contribute to these processes remain to be characterized. Four putative FOX TF genes were identified in the genome of M. oryzae, and phylogenetic analysis suggested that two of them (MoFKH1 and MoHCM1) correspond to Ascomycota-specific members of the FOX TF family while the others (MoFOX1 and MoFOX2) are Pezizomycotina-specific members. Deletion of MoFKH1 (${\Delta}Mofkh1$) resulted in reduced mycelial growth and conidial germination, abnormal septation and stress response, and reduced virulence. Similarly, ${\Delta}Mohcm1$ exhibited reduced mycelial growth and conidial germination. Conidia of ${\Delta}Mofkh1$ and ${\Delta}Mohcm1$ were more sensitive to one or both of the cell cycle inhibitors hydroxyurea and benomyl, suggesting their role in cell cycle control. On the other hand, loss of MoFOX1 (${\Delta}Mofox1$) did not show any noticeable changes in development, pathogenicity, and stress response. Deletion of MoFOX2 was not successful even after repeated attempts. Taken together, these results suggested that MoFKH1 and MoHCM1 are important in fungal development and that MoFKH1 is further implicated in pathogenicity and stress response in M. oryzae.