• Title/Summary/Keyword: translation initiation

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Effect of cell growth inhibition by eukaryotic initiation factor 2 derived peptides (진핵생물 개시인자 유래 펩타이드의 세포 성장 억제 효능)

  • Yu, HanJin;Lim, Kwang Suk
    • Journal of Industrial Technology
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    • v.40 no.1
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    • pp.1-6
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    • 2020
  • In the process of protein transcription and translation, various protein complexes bind to DNA, and all processes are precisely controlled. Among the proteins constituting this complex, a peptide derived from eukaryotic initiation factor (eIF) 2 was synthesized. In addition, in order to increase the efficiency of transduction of this peptide into cells, peptides with polyarginine, one of the protein transduction domains (PTD), were synthesized. Cell growth inhibition was confirmed in HER2 positive breast cancer (SK-Br-3) and HER2 negative breast cancer (MDA-MB-231), and cardiomyocytes (H9c2). The peptide with polyarginine had high transduction efficiency in all cells, and had excellent cancer cell growth inhibitory effects. The peptide used in this study might be useful peptide therapeutics for the treatment of cancer through future research.

Effect of Orally Administered Branched-chain Amino Acids on Protein Synthesis and Degradation in Rat Skeletal Muscle

  • Yoshizawa, Fumiaki;Nagasawa, Takashi;Sugahara, Kunio
    • Asian-Australasian Journal of Animal Sciences
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    • v.18 no.1
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    • pp.133-140
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    • 2005
  • Although amino acids are substrates for the synthesis of proteins and nitrogen-containing compounds, it has become more and more clear over the years that these nutrients are also extremely important as regulators of body protein turnover. The branched-chain amino acids (BCAAs) together or simply leucine alone stimulate protein synthesis and inhibit protein breakdown in skeletal muscle. However, it was only recently that the mechanism(s) involved in the regulation of protein turnover by BCAAs has begun to be defined. The acceleration of protein synthesis by these amino acids seems to occur at the level of peptide chain initiation. Oral administration of leucine to food-deprived rats enhances muscle protein synthesis, in part, through activation of the mRNA binding step of translation initiation. Despite our knowledge of the induction of protein synthesis by BCAAs, there are few studies on the suppression of protein degradation. The recent findings that oral administration of leucine rapidly reduced $N^{\tau}$-methylhistidine (3-methylhistidine; MeHis) release from isolated muscle, an index of myofibrillar protein degradation, indicate that leucine suppresses myofiblilar protein degradation. The details of the molecular mechanism by which leucine inhibits proteolysis is just beginning to be elucidated. The purpose of this report was to review the current understanding of how BCAAs act as regulators of protein turnover.

Role of E2F1 in Endoplasmic Reticulum Stress Signaling

  • Park, Kyung Mi;Kim, Dong Joon;Paik, Sang Gi;Kim, Soo Jung;Yeom, Young Il
    • Molecules and Cells
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    • v.21 no.3
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    • pp.356-359
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    • 2006
  • The transcription factor E2F1 coordinates cell cycle progression and induces apoptosis in response to DNA damage stress. Aside from DNA damage, the role of E2F1 in the endoplasmic reticulum (ER) stress signaling pathways is unclear. We found that $E2F1^{-/-}$ murine embryonic fibroblasts (MEFs) are resistant to apoptosis triggered by the ER stress inducer thapsigargin. In addition, E2F1 deficiency results in enhanced phosphorylation of eukaryotic translation initiation factor $2{\alpha}$ ($elF2{\alpha}$). These results therefore indicate that E2F1 deficiency increases phosphorylation of $elF2{\alpha}$ in response to ER stress triggered by thapsigargin, and suggest that the reduction in ER stress-induced apoptosis in E2F1-deficient cells is related to the high level of $elF2{\alpha}$ phosphorylation.

Influence of non-Gaussian characteristics of wind load on fatigue damage of wind turbine

  • Zhu, Ying;Shuang, Miao
    • Wind and Structures
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    • v.31 no.3
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    • pp.217-227
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    • 2020
  • Based on translation models, both Gaussian and non-Gaussian wind fields are generated using spectral representation method for investigating the influence of non-Gaussian characteristics and directivity effect of wind load on fatigue damage of wind turbine. Using the blade aerodynamic model and multi-body dynamics, dynamic responses are calculated. Using linear damage accumulation theory and linear crack propagation theory, crack initiation life and crack propagation life are discussed with consideration of the joint probability density distribution of the wind direction and mean wind speed in detail. The result shows that non-Gaussian characteristics of wind load have less influence on fatigue life of wind turbine in the area with smaller annual mean wind speeds. Whereas, the influence becomes significant with the increase of the annual mean wind speed. When the annual mean wind speeds are 7 m/s and 9 m/s at hub height of 90 m, the crack initiation lives under softening non-Gaussian wind decrease by 10% compared with Gaussian wind fields or at higher hub height. The study indicates that the consideration of the influence of softening non-Gaussian characteristics of wind inflows can significantly decrease the fatigue life, and, if neglected, it can result in non-conservative fatigue life estimates for the areas with higher annual mean wind speeds.

Backbone 1H, 15N, and 13C resonance assignments and secondary structure prediction of SAV2228 (translation initiation factor-1) from Staphylococcus aureus

  • Kim, Do-Hee;Jang, Sun-Bok;Lee, Bong-Jin
    • Journal of the Korean Magnetic Resonance Society
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    • v.16 no.2
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    • pp.162-171
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    • 2012
  • SAV2228 has an OB (Oligomer-Binding)-motif which is frequently used for nucleic acid recognition. To characterize the activity of translation initiation factor-1 (IF-1) from Staphylococcus aureus, SAV2228 was expressed and purified in Escherichia coli. We acquired 3D NMR spectra showing well dispersed and homogeneous signals which allow us to assign 94.4% of all $^1HN$, $^{15}N$, $^{13}C{\alpha}$, $^{13}C{\beta}$ and $^{13}CO$ resonances. We could predict a secondary structure of SAV2228 using TALOS and CSI from NMR data. SAV2228 was consisted of one ${\alpha}$-helix and five ${\beta}$-sheets. The predicted secondary structure, ${\beta}-{\beta}-{\beta}-{\alpha}-{\beta}-{\beta}$, was similar to other bacterial IF-1, but it was not completely same to the eukaryotic one. Assigned NMR peaks and secondary structre prediction can be used for the study on interaction with nucleic acid in the future.

Mutational Analyses of Translation Initiation Factor eIF1A in Saccharomyces cerevisiae (Saccharomyces cerevisiae에서 번역 개시 인자 eIF1A 돌연변이에 대한 분석)

  • Kwon, Sung-Hun;Kim, Jun-Ho;Choi, Bo-Kyung;Kim, Na-Yeon;Choi, Do-Hee;Park, Kyoung-Jun;Eoh, Jung-Hyun;Bae, Sung-Ho
    • Korean Journal of Microbiology
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    • v.45 no.3
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    • pp.239-245
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    • 2009
  • Translation initiation factor eIF1A performs essential functions in various initiation steps including 43S preinitiation complex formation in eukaryotes, and contains a highly conserved oligonucleotide-binding (OB) fold. In our previous study, we discovered that eIF1A possesses RNA annealing activity and forms a stable complex with double-stranded RNA. In this study, we initiated site-directed mutations in eIF1A to find the active sites for these biochemical activities and to investigate whether they are essential functions for yeast cell growth. A truncated protein, eIF1A($\Delta$T), devoid of both N- and C-terminal domains but containing an intact OB-fold exhibited RNA annealing activity. In contrast, all point mutations in OB-fold domain, except R57D, impaired both RNA annealing and dsRNA binding activities, indicating that the intact OB-fold domain is required for both activities. Viabilities of the mutant yeast cells were not correlated with RNA annealing activity but with the in vivo protein stabilities in the case of R57D and K94D.

Functional Equivalence of Translation Factor elF5B from Candida albicans and Saccharomyces cerevisiae

  • Jun, Kyung Ok;Yang, Eun Ji;Lee, Byeong Jeong;Park, Jeong Ro;Lee, Joon H.;Choi, Sang Ki
    • Molecules and Cells
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    • v.25 no.2
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    • pp.172-177
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    • 2008
  • Eukaryotic translation initiation factor 5B (eIF5B) plays a role in recognition of the AUG codon in conjunction with translation factor eIF2, and promotes joining of the 60S ribosomal subunit. To see whether the eIF5B proteins of other organisms function in Saccharomyces cerevisiae, we cloned the corresponding genes from Oryza sativa, Arabidopsis thaliana, Aspergillus nidulans and Candida albican and expressed them under the control of the galactose-inducible GAL promoter in the $fun12{\Delta}$ strain of Saccharomyces cerevisiae. Expression of Candida albicans eIF5B complemented the slow-growth phenotype of the $fun12{\Delta}$ strain, but that of Aspergillus nidulance did not, despite the fact that its protein was expressed better than that of Candida albicans. The Arabidopsis thaliana protein was also not functional in Saccharomyces. These results reveal that the eIF5B in Candida albicans has a close functional relationship with that of Sacharomyces cerevisiae, as also shown by a phylogenetic analysis based on the amino acid sequences of the eIF5Bs.

Investigation of Conserved Genes in Eukaryotes Common to Prokaryotes (원핵생물과 공통인 진핵생물의 보존적 유전자 탐색)

  • Lee, Dong-Geun
    • Journal of Life Science
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    • v.23 no.4
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    • pp.595-601
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    • 2013
  • The clusters of orthologous groups of proteins (COG) algorithm was applied to identify essential proteins in eukaryotes and to measure the degree of conservation. Sixty-three orthologous groups, which were conserved in 66 microbial genomes, enlarged to 104 eukaryotic orthologous groups (KOGs) and 71 KOGs were conserved at the nuclear genome of 7 eucaryotes. Fifty-four of 71 translation-related genes were conserved, highlighting the importance of proteins in modern organisms. Translation initiation factors (KOG0343, KOG3271) and prolyl-tRNA synthetase (KOG4163) showed high conservation based on the distance value analysis. The genes of Caenorhabditis elegans appear to harbor high genetic variation because the genome showed the highest variation at 71 conserved proteins among 7 genomes. The 71 conserved genes will be valuable in basic and applied research, for example, targeting for antibiotic development.

Phosphoinositide 3-kinase regulates myogenin expression at both the transcriptional and post-transcriptional level during myogenesis

  • Woo, Joo-Hong;Kim, Min-Jeong;Kim, Hye-Sun
    • Animal cells and systems
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    • v.14 no.3
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    • pp.147-154
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    • 2010
  • It is well-established that phosphoinositide 3-kinase (PI3-kinase) regulates myogenesis by inducing transcription of myogenin, a key muscle regulatory factor, at the initiation of myoblast differentiation. In this study, we investigated the role of PI3-kinase in cells that have committed to differentiation. PI3-kinase activity increases during myogenesis, and this increase is sustained during the myogenic process; however, its function after the induction of differentiation has not been investigated. We show that LY294002, a PI3-kinase inhibitor, blocked myoblast fusion even after myogenin expression initially increased. In contrast to the inhibitory effects of LY294002 on myogenin mRNA levels during the initiation of differentiation, LY294002 blocked the accumulation of myogenin protein without affecting its mRNA level after differentiation was induced. Treatment with cycloheximide, a translation inhibitor, or actinomycin D, a transcription inhibitor, indicated that the stability of myogenin protein is lower than that of its mRNA. LY294002 inhibited the activities of several important translation factors, including eukaryotic elongation factor-2(eEF2), by altering their phosphorylation status. In addition, LY294002 blocked the incorporation of [$^{35}S$]methionine into newly synthesized proteins. Since myogenin has a relatively short half-life, LY294002-mediated inhibition of post-transcriptional processes resulted in a rapid depletion of myogenin protein. In summary, these results suggest that PI3-kinase plays an important role in regulating the expression of myogenin through post-transcriptional mechanisms after differentiation has been induced.

The Role of Intracellular Signaling Pathways in the Neurobiology of the Depressive Disorder (우울장애의 신경생물학적 기전으로서 세포 내 신호전달계의 역할)

  • Kim, Se-Hyun
    • Korean Journal of Biological Psychiatry
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    • v.18 no.4
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    • pp.189-196
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    • 2011
  • Major depressive disorder is characterized by cellular and molecular alterations resulting in the depressive behavioral phenotypes. Preclinical and clinical studies have demonstrated the deficits, including cell atrophy and loss, in limbic and cortical regions of patients with depression, which is restored with antidepressants by reestablishing proper molecular changes. These findings have implicated the involvement of relevant intracellular signaling pathways in the pathogenetic and therapeutic mechanisms of depressive disorders. This review summarizes the current knowledge of the signal transduction mechanisms related to depressive disorders, including cyclic-AMP, mitogen-activated protein kinase, Akt, and protein translation initiation signaling cascades. Understanding molecular components of signaling pathways regulating neurobiology of depressive disorders may provide the novel targets for the development of more efficacious treatment modalities.