• Title/Summary/Keyword: Molecular pathway

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The Arabidopsis AtLEC Gene Encoding a Lectin-like Protein Is Up-Regulated by Multiple Stimuli Including Developmental Signal, Wounding, Jasmonate, Ethylene, and Chitin Elicitor

  • Lyou, Seoung Hyun;Park, Hyon Jin;Jung, Choonkyun;Sohn, Hwang Bae;Lee, Garam;Kim, Chung Ho;Kim, Minkyun;Choi, Yang Do;Cheong, Jong-Joo
    • Molecules and Cells
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    • v.27 no.1
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    • pp.75-81
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    • 2009
  • The Arabidopsis gene AtLEC (At3g15356) gene encodes a putative 30-kDa protein with a legume lectin-like domain. Likely to classic legume lectin family of genes, AtLEC is expressed in rosette leaves, primary inflorescences, and roots, as observed in Northern blot analysis. The accumulation of AtLEC transcript is induced very rapidly, within 30 min, by chitin, a fungal wall-derived oligosaccharide elictor of the plant defense response. Transgenic Arabidopsis carrying an AtLEC promoter-driven ${\beta}$-glucuronidase (GUS) construct exhibited GUS activity in the leaf veins, secondary inflorescences, carpel heads, and silique receptacles, in which no expression could be seen in Northern blot analysis. This observation suggests that AtLEC expression is induced transiently and locally during developmental processes in the absence of an external signal such as chitin. In addition, mechanically wounded sites showed strong GUS activity, indicating that the AtLEC promoter responds to jasmonate. Indeed, methyl jasmonate and ethylene exposure induced AtLEC expression within 3-6 h. Thus, the gene appears to play a role in the jasmonate-/ethylene-responsive, in addition to the chitin-elicited, defense responses. However, chitin-induced AtLEC expression was also observed in jasmonate-insensitive (coi1) and ethylene-insensitive (etr1-1) Arabidopsis mutants. Thus, it appears that chitin promotes AtLEC expression via a jasmonate- and/or ethylene-independent pathway.

Crystal Structures of Substrate and Inhibitor Complexes of Ribose 5-Phosphate Isomerase A from Vibrio vulnificus YJ016

  • Kim, Tae Gyun;Kwon, Taek Hun;Min, Kyoungin;Dong, Mi-Sook;Park, Young In;Ban, Changill
    • Molecules and Cells
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    • v.27 no.1
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    • pp.99-103
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    • 2009
  • Ribose-5-phosphate isomerase A (RpiA) plays an important role in interconverting between ribose-5-phosphate (R5P) and ribulose-5-phosphate in the pentose phosphate pathway and the Calvin cycle. We have determined the crystal structures of the open form RpiA from Vibrio vulnificus YJ106 (VvRpiA) in complex with the R5P and the closed form with arabinose-5-phosphate (A5P) in parallel with the apo VvRpiA at $2.0{\AA}$ resolution. VvRpiA is highly similar to Escherichia coli RpiA, and the VvRpiA-R5P complex strongly resembles the E. coli RpiA-A5P complex. Interestingly, unlike the E. coli RpiA-A5P complex, the position of A5P in the VvRpiA-A5P complex reveals a different position than the R5P binding mode. VvRpiA-A5P has a sugar ring inside the binding pocket and a phosphate group outside the binding pocket: By contrast, the sugar ring of A5P interacts with the Asp4, Lys7, Ser30, Asp118, and Lys121 residues; the phosphate group of A5P interacts with two water molecules, W51 and W82.

Regulation of Ethylene Biosynthesis by Phytohormones in Etiolated Rice (Oryza sativa L.) Seedlings

  • Lee, Han Yong;Yoon, Gyeong Mee
    • Molecules and Cells
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    • v.41 no.4
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    • pp.311-319
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    • 2018
  • The gaseous hormone ethylene influences many aspects of plant growth, development, and responses to a variety of stresses. The biosynthesis of ethylene is tightly regulated by various internal and external stimuli, and the primary target of the regulation is the enzyme 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS), which catalyzes the rate-limiting step of ethylene biosynthesis. We have previously demonstrated that the regulation of ethylene biosynthesis is a common feature of most of the phytohormones in etiolated Arabidopsis seedlings via the modulation of the protein stability of ACS. Here, we show that various phytohormones also regulate ethylene biosynthesis from etiolated rice seedlings in a similar manner to those in Arabidopsis. Cytokinin, brassinosteroids, and gibberellic acid increase ethylene biosynthesis without changing the transcript levels of neither OsACS nor ACC oxidases (OsACO), a family of enzymes catalyzing the final step of the ethylene biosynthetic pathway. Likewise, salicylic acid and abscisic acid do not alter the gene expression of OsACS, but both hormones downregulate the transcript levels of a subset of ACO genes, resulting in a decrease in ethylene biosynthesis. In addition, we show that the treatment of the phytohormones results in distinct etiolated seedling phenotypes, some of which resemble ethylene-responsive phenotypes, while others display ethylene-independent morphologies, indicating a complicated hormone crosstalk in rice. Together, our study brings a new insight into crosstalk between ethylene biosynthesis and other phytohormones, and provides evidence that rice ethylene biosynthesis could be regulated by the post-transcriptional regulation of ACS proteins.

The Role of Nuclear Receptor Subfamily 1 Group H Member 4 (NR1H4) in Colon Cancer Cell Survival through the Regulation of c-Myc Stability

  • Lee, Yun Jeong;Lee, Eun-Young;Choi, Bo Hee;Jang, Hyonchol;Myung, Jae-Kyung;You, Hye Jin
    • Molecules and Cells
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    • v.43 no.5
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    • pp.459-468
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    • 2020
  • Nuclear receptor subfamily group H member 4 (NR1H4), also known as farnesoid X receptor, has been implicated in several cellular processes in the liver and intestine. Preclinical and clinical studies have suggested a role of NR1H4 in colon cancer development; however, how NR1H4 regulates colon cancer cell growth and survival remains unclear. We generated NR1H4 knockout (KO) colon cancer cells using clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (CAS9) technology and explored the effects of NR1H4 KO in colon cancer cell proliferation, survival, and apoptosis. Interestingly, NR1H4 KO cells showed impaired cell proliferation, reduced colony formation, and increased apoptotic cell death compared to control colon cancer cells. We identified MYC as an important mediator of the signaling pathway alterations induced by NR1H4 KO. NR1H4 silencing in colon cancer cells resulted in reduced MYC protein levels, while NR1H4 activation using an NR1H4 ligand, chenodeoxycholic acid, resulted in time- and dose-dependent MYC induction. Moreover, NR1H4 KO enhanced the anti-cancer effects of doxorubicin and cisplatin, supporting the role of MYC in the enhanced apoptosis observed in NR1H4 KO cells. Taken together, our findings suggest that modulating NR1H4 activity in colon cancer cells might be a promising alternative approach to treat cancer using MYC-targeting agents.

3,4-Dihydroxytoluene Inhibits Epidermal Growth Factor-induced Cell Transformation in JB6 P+ Mouse Epidermal Cells by Suppressing Raf-1 (3,4-Dihydroxytoluene의 Raf-1 신호전달체계 억제를 통한 암예방 효능)

  • Kim, Ji An;Kim, Ji Hye;di Ruccio, Eric;Kang, Nam Joo
    • The Korean Journal of Food And Nutrition
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    • v.28 no.1
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    • pp.111-118
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    • 2015
  • In summary, the rutin metabolite DHT significantly reduced EGF-induced neoplastic transformation in JB6 P+ cells. This inhibition was mediated mainly by blocking the Raf/MEK/ERK signaling pathway and subsequent suppression of AP-1 activities. DHT attenuated Raf-1 kinase activity by directly binding to Raf-1 in vitro and ex vivo. Taken together, these results suggest that Raf-1 may be a critical molecular target to suppress DHT-induced neoplastic transformation, which is mainly attributable to the chemopreventive potential of several foods containing rutin.

An Anticoagulant Polysaccharide Isolated from the Alkali Extracts of Coriolus versicolor (구름버섯 알칼리 추출물에서 분리한 항응고성 다당류)

  • Lee, Hyun-Sun;Kweon, Mee-Hyang;Lim, Wang-Jin;Sung, Ha-Chin;Yang, Han-Chul
    • Korean Journal of Food Science and Technology
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    • v.29 no.2
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    • pp.369-375
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    • 1997
  • We have isolated an anticoagulant polysaccharide from the alkali extracts of Coriolus versicolor. The anticoagulant polysaccharide was purified through a gradual ethanol precipitation and three concecutive chromatography of DEAE-Toyopearl 650C, Sephadex G-100, and Sepharose CL-6B by measuring activated partial thromboplastin time (aPTT). The anticoagulant polysaccharide showed the homogenecity on HPLC using a gel permeation column and had about $7.2{\times}10^{5}$ molecular weight. The polysaccharide consisted of fucose, glucose, and galactose in a molar ratio of 1.0:0.2:0.2:0.1, and also compromised 19.32% of sulfate at its constituent sugars. The polysaccharide showed the two typical bands of C-O-S $(823\;cm^{-1})$ and S=O $(1257\;cm^{-1})$ in the IR spectroscopy. The sulfated polysaccharide (CV-40-Va-1) inhibited the blood coagulation via the intrinsic pathway like heparin whose activity produced a concentration dependent effect in aPTT and thrombin time (TT).

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Naesohwangryeon-tang Induced Apoptosis and Autophagy in A549 Human Lung Cancer Cells

  • Kim, Hong Jae;Jeong, Jin-Woo;Park, Cheol;Choi, Yung Hyun;Hong, Su Hyun
    • Journal of Pharmacopuncture
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    • v.22 no.4
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    • pp.269-278
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    • 2019
  • Objectives: Naesohwangryeon-tang (NHT) is a type of traditional herbal formula, however, little is known about its antitumor activity. In this study, the antitumor properties of NHT was evaluated in human lung adenocarcinoma cells. Methods: To check the inhibitory effect of NHT, MTT assay was performed. Cell cycle analysis and detection of ROS production were conducted by flow cytometry. To evaluate the signaling pathway, Western blotting was conducted. Results: Our results showed that the decrease of cell proliferation by NHT stimulation occurred more significantly in A549 cells than in NCI-H460 cells. In addition, NHT-induced apoptosis was associated with the activation of caspases and production of reactive oxygen species (ROS). NHT-induced apoptosis was attenuated after pretreatments with z-VAD-fmk or N-acetylcysteine, suggesting that NHT-induced apoptosis was caspaseand ROS-dependent. Interestingly, NHT treatment led to the development of autophagic vesicular organelles and upregulation of several autophagy-related genes. The pretreatment of bafilomycin A1 decreased apoptosis slightly but increased cell viability in the presence of NHT. Conclusion: These findings indicated that NHT induces both apoptosis and cell-protective autophagy in human lung cancer cells. This data suggests that NHT might be a novel herbal drug for lung cancer.

KUGI: A Database and Search System for Korean Unigene and Pathway Information

  • Yang, Jin-Ok;Hahn, Yoon-Soo;Kim, Nam-Soon;Yu, Ung-Sik;Woo, Hyun-Goo;Chu, In-Sun;Kim, Yong-Sung;Yoo, Hyang-Sook;Kim, Sang-Soo
    • Proceedings of the Korean Society for Bioinformatics Conference
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    • 2005.09a
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    • pp.407-411
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    • 2005
  • KUGI (Korean UniGene Information) database contains the annotation information of the cDNA sequences obtained from the disease samples prevalent in Korean. A total of about 157,000 5'-EST high throughput sequences collected from cDNA libraries of stomach, liver, and some cancer tissues or established cell lines from Korean patients were clustered to about 35,000 contigs. From each cluster a representative clone having the longest high quality sequence or the start codon was selected. We stored the sequences of the representative clones and the clustered contigs in the KUGI database together with their information analyzed by running Blast against RefSeq, human mRNA, and UniGene databases from NCBI. We provide a web-based search engine fur the KUGI database using two types of user interfaces: attribute-based search and similarity search of the sequences. For attribute-based search, we use DBMS technology while we use BLAST that supports various similarity search options. The search system allows not only multiple queries, but also various query types. The results are as follows: 1) information of clones and libraries, 2) accession keys, location on genome, gene ontology, and pathways to public databases, 3) links to external programs, and 4) sequence information of contig and 5'-end of clones. We believe that the KUGI database and search system may provide very useful information that can be used in the study for elucidating the causes of the disease that are prevalent in Korean.

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Current Mechanistic Approaches to the Chemoprevention of Cancer

  • Steele, Vernon E.
    • BMB Reports
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    • v.36 no.1
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    • pp.78-81
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    • 2003
  • The prevention of cancer is one of the most important public health and medical practices of the $21^{st}$ century. We have made much progress in this new emerging field, but so much remains to be accomplished before widespread use and practice become common place. Cancer chemoprevention encompasses the concepts of inhibition, reversal, and retardation of the cancer process. This process, called carcinogenesis, requires 20-40 years to reach the endpoint called invasive cancer. It typically follows multiple, diverse and complex pathways in a stochastic process of clonal evolution. These pathways appear amenable to inhibition, reversal or retardation at various points. We must therefore identify key pathways in the evolution of the cancer cell that can be exploited to prevent this carcinogenesis process. Basic research is identifying many genetic lesions and epigenetic processes associated with the progression of precancer to invasive disease. Many of these early precancerous lesions favor cell division over quiescence and protect cells against apoptosis when signals are present. Many oncogenes are active during early development and are reactivated in adulthood by aberrant gene promoting errors. Normal regulatory genes are mutated, making them insensitive to normal regulatory signals. Tumor suppressor genes are deleted or mutated rendering them inactive. Thus there is a wide range of defects in cellular machinery which can lead to evolution of the cancer phenotype. Mistakes may not have to appear in a certain order for cells to progress along the cancer pathway. To conquer this diverse disease, we must attack multiple key pathways at once for a predetermined period of time. Thus, agent combination prevention strategies are essential to decrease cancer morbidity. Furthermore, each cancer type may require custom combination of prevention strategies to be successful.

Inhibition of Adipocyte Differentiation by Anthocyanins Isolated from the Fruit of Vitis coignetiae Pulliat is Associated with the Activation of AMPK Signaling Pathway

  • Han, Min Ho;Kim, Hong Jae;Jeong, Jin-Woo;Park, Cheol;Kim, Byung Woo;Choi, Yung Hyun
    • Toxicological Research
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    • v.34 no.1
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    • pp.13-21
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    • 2018
  • Anthocyanins are naturally occurring water-soluble polyphenolic pigments in plants that have been shown to protect against cardiovascular diseases, and certain cancers, as well as other chronic human disorders. However, the anti-obesity effects of anthocyanins are not fully understood. In this study, we investigated the effects of anthocyanins isolated from the fruit of Vitis coignetiae Pulliat on the adipogenesis of 3T3-L1 preadipocytes. Our data indicated that anthocyanins attenuated the terminal differentiation of 3T3-L1 preadipocytes, as confirmed by a decrease in the number of lipid droplets, lipid content, and triglyceride production. During this process, anthocyanins effectively enhanced the activation of the AMP-activated protein kinase (AMPK); however, this phenomenon was inhibited by the co-treatment of compound C, an inhibitor of AMPK. Anthocyanins also inhibited the expression of adipogenic transcription factors, including peroxisome proliferator-activated receptor-${\gamma}$, CCAAT/enhancer-binding protein a and b, and sterol regulatory element-binding protein-1c. In addition, anthocyanins were found to potently inhibit the expression of adipocyte-specific genes, including adipocyte fatty acid-binding protein, leptin, and fatty acid synthase. These results indicate that anthocyanins have potent anti-obesity effects due to the inhibition of adipocyte differentiation and adipogenesis, and thus may have applications as a potential source for an anti-obesity functional food agent.