• Title/Summary/Keyword: Systems biology

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miR-185 inhibits endoplasmic reticulum stress-induced apoptosis by targeting Na+/H+ exchanger-1 in the heart

  • Kim, Jin Ock;Kwon, Eun Jeong;Song, Dong Woo;Lee, Jong Sub;Kim, Do Han
    • BMB Reports
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    • v.49 no.4
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    • pp.208-213
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    • 2016
  • Prolonged ER stress (ERS) can be associated with the induction of apoptotic cell death in various heart diseases. In this study, we searched for microRNAs affecting ERS in the heart using in silico and in vitro methods. We found that miR-185 directly targets the 3′-untranslated region of Na+/H+ exchanger-1 (NHE-1), a protein involved in ERS. Cardiomyocyte ERS-triggered apoptosis induced by 100 ng/ml tunicamycin (TM) or 1 μM thapsigargin (TG), ERS inducers, was significantly reduced by miR-185 overexpression. Protein expression of pro-apoptotic markers such as CCAAT/enhancer-binding protein homologous protein (CHOP) and cleaved-caspase-3 was also markedly reduced by miR-185 in a dose-dependent manner. Cariporide (20 μM), a pharmacological inhibitor of NHE-1, also attenuated ERS-induced apoptosis in cardiomyocytes and CHOP protein expression, suggesting that NHE-1 plays an important role in ERS-associated apoptosis in cardiomyocytes. Collectively, the present results demonstrate that miR-185 is involved in cardio-protection against ERS-mediated apoptotic cell death.

Integrative Profiling of Alternative Splicing Induced by U2AF1 S34F Mutation in Lung Adenocarcinoma Reveals a Mechanistic Link to Mitotic Stress

  • Kim, Suyeon;Park, Charny;Jun, Yukyung;Lee, Sanghyuk;Jung, Yeonjoo;Kim, Jaesang
    • Molecules and Cells
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    • v.41 no.8
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    • pp.733-741
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    • 2018
  • Mutations in spliceosome components have been implicated in carcinogenesis of various types of cancer. One of the most frequently found is U2AF1 S34F missense mutation. Functional analyses of this mutation have been largely limited to hematological malignancies although the mutation is also frequently seen in other cancer types including lung adenocarcinoma (LUAD). We examined the impact of knockdown (KD) of wild type (wt) U2AF1 and ectopic expression of two splice variant S34F mutant proteins in terms of alternative splicing (AS) pattern and cell cycle progression in A549 lung cancer cells. We demonstrate that induction of distinct AS events and disruption of mitosis at distinct sub-stages result from KD and ectopic expression of the mutant proteins. Importantly, when compared with the splicing pattern seen in LUAD patients with U2AF1 S34F mutation, ectopic expression of S34F mutants but not KD was shown to result in common AS events in several genes involved in cell cycle progression. Our study thus points to an active role of U2AF1 S34F mutant protein in inducing cell cycle dysregulation and mitotic stress. In addition, alternatively spliced genes which we describe here may represent novel potential markers of lung cancer development.

Characterization of calumenin in mouse heart

  • Sahoo, Sanjaya Kumar;Kim, Do-Han
    • BMB Reports
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    • v.43 no.3
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    • pp.158-163
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    • 2010
  • Calumenin is a multiple EF-hand $Ca^{2+}$-binding protein located in the endo/sarcoplasmic reticulum of mammalian hearts. Calumenin belongs to the CREC family of $Ca^{2+}$-binding proteins having multiple EF-hands. $Ca^{2+}$ homeostasis in the sarcoplasmic reticulum (SR) of mammalian hearts is maintained by RyR2, SERCA2 and other associated SR resident proteins. Evidence suggests that calumenin interacts with RyR2 and SERCA2, and therefore changes in the expression of calumenin could alter $Ca^{2+}$ cycling in mouse heart. In this review, current knowledge of the biochemical and functional roles of calumenin in mouse heart is described.

Structural insights showing how arginine is able to be glycosylated by pathogenic effector proteins

  • Park, Jun Bae;Yoo, Youngki;Cho, Hyun-Soo
    • BMB Reports
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    • v.51 no.12
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    • pp.609-610
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    • 2018
  • Glycosylation is one form of protein modification and plays a key role in protein stability, function, signaling regulation and even cancer. NleB and SseK are bacterial effector proteins and possess glycosyltransferase activity, even though they have different substrate preferences. NleB/SseKs transfer the GlcNAc sugar to an arginine residue of host proteins, leading to reduced $NF-{\kappa}B-dependent$ responses. By combining X-ray crystallography, NMR, molecular dynamics, enzyme kinetic assays and in vivo experiments, we demonstrated that a conserved HEN (His-Glu-Asn) motif in the active site plays a key role in enzyme catalysis and virulence. The lid-domain regulates the opening and closing of the active site and the HLH domain determines the substrate specificity. Our findings provide evidence for the enzymatic mechanism by which arginine can be glycosylated by SseK/NleB enzymes.

Epigenetic aspects of telomeric chromatin in Arabidopsis thaliana

  • Lee, Won Kyung;Cho, Myeon Haeng
    • BMB Reports
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    • v.52 no.3
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    • pp.175-180
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    • 2019
  • Telomeres are nucleoprotein complexes at the physical ends of linear eukaryotic chromosomes. They protect the chromosome ends from various external attacks to avoid the loss of genetic information. Telomeres are maintained by cellular activities associated with telomerase and telomere-binding proteins. In addition, epigenetic regulators have pivotal roles in controlling the chromatin state at telomeres and subtelomeric regions, contributing to the maintenance of chromosomal homeostasis in yeast, animals, and plants. Here, we review the recent findings on chromatin modifications possibly associated with the dynamic states of telomeres in Arabidopsis thaliana.

Distribution of Microzooplankton across the Frontal Systems of the Southern Ocean

  • Lee, Hak-Young;Cho, In-Sook;Kim, Jong-Won;Richard M. Greene
    • Environmental Sciences Bulletin of The Korean Environmental Sciences Society
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    • v.3 no.1
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    • pp.1-9
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    • 1999
  • Microzooplankton was analysed between $40^{\circ}s$ to $53^{\circ}s$S and $140^{\circ}E$ to $146^{\circ}E$ of the Sourthern Ocean from November 18 to November 30, 1995 to investigate the influence of frontal systems. The density and carbon biomass of microzooplankton were clearly associated with frontal systems, and at least 4 different communities were identified. The Subtropical Convergence Zone and Antarctic Polar Front Zone were the major biological boundaries recognized in the Southern Ocean. Ciliates predominated other microzooplankton in density and carbon biomass. Non-tintinnid ciliates occupied more than 70% of the total microzooplankton, and Laboea spp. was the major component of the non-tintinnid ciliates. The density and carbon biomass showed a decreasing tendency toward south from $40^{\circ}S$ to the $53^{\circ}S$ transect. The ecological importance of a frontal zone is confirmed by the microzooplanktonic data obtained from this study.

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