• 제목/요약/키워드: the transcription factors

검색결과 1,098건 처리시간 0.035초

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
    • /
    • 제15권2호
    • /
    • pp.551-560
    • /
    • 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
    • /
    • 제28권1호
    • /
    • pp.40-48
    • /
    • 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.

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

  • 이기전;김복규;길기정
    • 대한본초학회지
    • /
    • 제28권1호
    • /
    • pp.33-42
    • /
    • 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.

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

  • 이영기;김성례
    • Clinical and Experimental Reproductive Medicine
    • /
    • 제25권3호
    • /
    • pp.305-313
    • /
    • 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.

  • PDF

Post-Translational Regulations of Transcriptional Activity of RUNX2

  • Kim, Hyun-Jung;Kim, Woo-Jin;Ryoo, Hyun-Mo
    • Molecules and Cells
    • /
    • 제43권2호
    • /
    • pp.160-167
    • /
    • 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.

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

  • 김범수
    • 한국발생생물학회지:발생과생식
    • /
    • 제14권2호
    • /
    • pp.75-82
    • /
    • 2010
  • 이 연구는 제2형 당뇨 모델 동물인 Goto-Kakizaki(GK) 흰쥐를 사용하여 운동과 셀레늄 투여가 미토콘드리아 생성과 기능 향상을 조절하는 전사 인자의 발현 변화와 현상학적으로 당뇨의 증상 개선을 유도할 수 있는지를 구명하기 위해 실시하였다. 실험동물은 52주령된 GK 수컷 흰쥐로 24 m/min, 30 min/day, 5 days/week, 총 6주간 트레드밀 런닝을 실시하였다. Sodium selenite(5 umol/kg)는 selenium 집단과 combination 집단에 1주일에 5일씩 6주간 복강에 주입하였다. 운동과 셀레늄 투여는 미토콘드리아의 생성에 관여하는 peroxisome proliferators-activated receptor gamma coactivator-1alpha(PGC-$1{\alpha}$), nuclear respiratory factors(NRF-1), 그리고 mitochondrial transcription factor A(Tfam) 발현을 증가시켰으며, 그 결과로 미토콘드리아량의 지표 단백질인 cytochrome C도 증가를 보였다. 특히, 운동이나 셀레늄의 단독적인 처치보다는 운동과 셀레늄 병행 처치가 미토콘드리아의 생성 및 활성 증가, 그리고 포도당 내성에 긍정적인 효과를 보였다. 따라서, 본 연구에서 수행된 운동과 셀레늄 투여 처치는 당뇨의 개선 효과 및 당뇨 질환과 관련된 미토콘드리아의 기능 향상에 긍정적인 효과를 보이는 것으로 나타났다.

Overexpression of OsNAC17 enhances drought tolerance in rice

  • Kim, Tae Hwan;Kim, Ju-Kon
    • 한국작물학회:학술대회논문집
    • /
    • 한국작물학회 2017년도 9th Asian Crop Science Association conference
    • /
    • pp.168-168
    • /
    • 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

  • PDF

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

  • 장혜영;김재호
    • 생명과학회지
    • /
    • 제15권6호
    • /
    • pp.928-934
    • /
    • 2005
  • ATF2는 c-Fos와 c-Jun과 같은 전사인자이며 이들은 루신지퍼 단백질이다. 루신지퍼 단백질은 동형이합체 혹은 이형이합체를 형성하며 promoter 영역에 결합하여 전사조절에 중요한 역할을 한다. 세포의 전사인자 ATF2는 ATF/CRE site에 결합하며 특히 선택적인 interfamily 이형이량체를 형성함으로써 전사 조절에 있어서 다양한 메카니즘을 제공할 수 있다. 본 연구에서는 ATF2 cDNA를 6xHis를 가진 expression vector에 subcloning하여 E.cnli BL2l에서 발현시켰다. 6xHis tag은 nickel-chelating chromatography를 가능하게 하였다 발현된 ATF2는 In vitro binding pull-down assay에서 동형이합체를 이를 뿐만 아니라 AP-1 그룹의 인자들과 선택적인 이형이합체를 형성함을 보여 주었다. BATF와는 강하게 결합하였으며 c-Jun과도 안정된 이합체를 형성하였다. 그러나 c-Fos와는 이합체를 형성하지 않으므로서 AP-1그룹 내에서도 이합체 형성이 선택적으로 이루어짐을 알 수 있다.

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
    • /
    • 제30권2호
    • /
    • pp.136-150
    • /
    • 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.