• Title/Summary/Keyword: 4EBP1

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Developmental Expression of Eukaryotic Initiation Factor 4E (eIF4E) and eIF4E-binding Protein 1 (eIF4EBP1) in Rat Hippocampal Neurons (발생단계별 해마신경세포에서 eIF4E 및 eIF4EBP1의 표현)

  • Park, Jaewan;Moon, Il Soo
    • Journal of Life Science
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    • v.23 no.7
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    • pp.941-946
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    • 2013
  • Local protein synthesis at subsynaptic sites plays a key role in the regulation of the protein composition in local domains. In this study, we carried out immunocytochemistry of cultured rat hippocampal neurons in various developmental stages to investigate the expression of eIF4E and its binding protein, eIF4EBP1. Both proteins were distributed in dendrites. In addition, eIF4EBP1 was highly expressed in the nucleus throughout the development, whereas eIF4E was not expressed in the nucleus. Punctate expression of eIF4E and eIF4EBP1 was evident in DIV 3. The colocalization rates of eIF4E or eIF4EBP1 puncta with PSD95 were higher in the dendrogenic than in the mature stages. In contrast, the colocalization rates of eIF4E and eIF4EBP1 puncta were higher in the mature than in the dendrogenic stages. As eIF4E is inactive when it is bound to eIF4EBP1, these data indicate that most dendritic eIF4E's are active during development but that they are mostly under inhibition in mature neurons.

ErbB3 binding protein 1 contributes to adult hippocampal neurogenesis by modulating Bmp4 and Ascl1 signaling

  • Youngkwan Kim;Hyo Rim Ko;Inwoo Hwang;Jee-Yin Ahn
    • BMB Reports
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    • v.57 no.4
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    • pp.182-187
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    • 2024
  • Neural stem cells (NSCs) in the adult hippocampus divide infrequently; the endogenous molecules modulating adult hippocampal neurogenesis (AHN) remain largely unknown. Here, we show that ErbB3 binding protein 1 (Ebp1), which plays important roles in embryonic neurodevelopment, acts as an essential modulator of adult neurogenic factors. In vivo analysis of Ebp1 neuron depletion mice showed impaired AHN with a low number of hippocampal NSCs and neuroblasts. Ebp1 leads to transcriptional repression of Bmp4 and suppression of Ascl1 promoter methylation in the dentate gyrus of the adult hippocampus reflecting an unusually high level of Bmp4 and low Ascl1 level in neurons of Ebp1-deficient mice. Therefore, our findings suggests that Ebp1 could act as an endogenous modulator of the interplay between Bmp4 and Ascl1/Notch signaling, contributing to AHN.

Regulatory Mechanism in Tissue-specific Expression of Insulin-like Growth Factor-I Gene (Insulin-like growth factor-I 유전자의 조직 특이적 발현에 대한 조절기전)

  • 안미라
    • KSBB Journal
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    • v.18 no.4
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    • pp.329-334
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    • 2003
  • The present study was aimed at investigating the regulatory mechanism in tissue-specific expression of insulin-like growth factor-I (IGF-I) gene. The expression of IGF-I gene was determined by a solution hybridization/RNase protection assay using total RNA prepared from rat liver or brain of various ages. The levels of IGF-I transcripts were increased in liver gradually after birth, but decreased in brain. By using an oligonucleotide (FRE) corresponding to the C/EBP binding site of the rat IGF-I exon 1, multiple forms of C/EBP${\alpha}$ and C/EBP${\beta}$ proteins, which have DNA-binding activity, were detected in the rat liver or brain. Western immunoblot and southwestern analyses show that p42$\^$C/EBP${\alpha}$/, p38$\^$C/EBP${\alpha}$/, p35$\^$C/EBP${\alpha}$/, p38$\^$C/EBP${\beta}$/, and p35$\^$C/EBP${\beta}$ form specific complexes with the IGF-I exon 1 oligonucleotide in liver nuclear extract and that p42$\^$C/EBP${\alpha}$/ and p38$\^$C/EBP${\beta}$/ form complexes in brain. These data suggest that the formation of FRE-C/EBP isoform complexes may play important roles in the tissue-specific regulation of IGF-I gene expression.

TonEBP suppresses adipocyte differentiation via modulation of early signaling in 3T3-L1 cells

  • Kim, Soo Jin;Kim, Taehee;Choi, Han Na;Cho, Eun Jung;Park, Jin Bong;Jeon, Byeong Hwa;Lee, Sang Do
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.6
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    • pp.649-655
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    • 2016
  • TonEBP belongs to the Rel family of transcription factors and plays important roles in inflammation as well as kidney homeostasis. Recent studies suggest that TonEBP expression is also involved in differentiation of several cell types such as myocytes, chondrocytes, and osteocytes. In this study, we investigated the roles of TonEBP during adipocyte differentiation in 3T3-L1 cells. TonEBP mRNA and protein expression was dramatically reduced during adipocyte differentiation. Sustained expression of TonEBP using an adenovirus suppressed the formation of lipid droplets as well as the expression of FABP4, a marker of differentiated adipocytes. TonEBP also inhibited the expression of $PPAR{\gamma}$, a known master regulator of adipocytes. RNAi-mediated knock down of TonEBP promoted adipocyte differentiation. However, overexpression of TonEBP did not affect adipogenesis after the initiation of differentiation. Furthermore, TonEBP expression suppressed mitotic clonal expansion and insulin signaling, which are required early for adipocyte differentiation of 3T3-L1 cells. These results suggest that TonEBP may be an important regulatory factor in the early phase of adipocyte differentiation.

Silibinin Inhibits Adipogenesis and Induces Apoptosis in 3T3-L1 Adipocytes (Silibnin의 지방세포분화 억제 및 세포사멸 유도 효과)

  • Lee, Seul Gi;Kwon, Taeg Kyu;Nam, Ju-Ock
    • Microbiology and Biotechnology Letters
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    • v.45 no.1
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    • pp.27-34
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    • 2017
  • $C/EBP{\beta}$ and $C/EBP{\delta}$ are required for the initiation of adipogenesis and induce the expression of key adipogenic regulators, such as $PPAR{\gamma}$ and $C/EBP{\alpha}$. In the present study, we have examined the effects of silibinin and its possible molecular mechanisms in regulating adipocyte differentiation and expression of $C/EBP{\beta}$ and $C/EBP{\delta}$ in the early stage of adipogenesis. Silibinin statistically significantly inhibits intracellular lipid accumulation and the mRNA expression of various genes involved at different stages during adipogenesis. Silibinin also suppresses expression of lipoprotein lipase (LPL), fatty acid binding protein 4 (AP2), and adiponectin in 3T3-L1 adipocytes. Thus, the anti-adipogenic effect of silibinin seems to originate from the ability to inhibit the expression of $C/EBP{\beta}$ and $C/EBP{\delta}$. Furthermore, silibinin decreases cell viability for differentiation period and induces apoptotic cell death through capspase-3 activation.

Detergent Screening for NMR-Based Structural Study of the Integral Membrane Protein, Emopamil Binding Protein (Human Sterol Δ8-Δ7 Isomerase)

  • Won, Hyung-Sik
    • Journal of the Korean Magnetic Resonance Society
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    • v.21 no.1
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    • pp.13-19
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    • 2017
  • Human sterol ${\Delta}8-{\Delta}7$ isomerase, commonly known as emopamil binding protein (EBP), is an essential protein in the cholesterol-synthetic pathway, and mutations of this protein are critically associated with human diseases such as Conradi-Hunermann-Happle or male EBP disorder with neurological defects syndrome. Due to such a clinical importance, EBP has been intensively investigated and some important features have been reported. EBP is a tetra-spanning membrane protein, of which $2^{nd}$, $3^{rd}$, and $4^{th}$ membrane-spanning ${\alpha}$ helices play an important role in its enzymatic function. However, detailed structural feature at atomic resolution has not yet been elucidated, due to characteristic difficulties in dealing with membrane protein. Here, we over-expressed EBP using Escherichia coli and performed detergent screening to find suitable membrane mimetics for structural studies of the protein by NMR. As results, DPC and LMPG could be evaluated as the most favorable detergents to acquire promising NMR spectra for structural study of EBP.

Ectopic EBP2 expression enhances cyclin E1 expression and induces chromosome instability in HEK293 stable clones

  • Lee, Ming-Cheng;Hsieh, Chang-Hsun;Wei, Shu-Chen;Shen, Shu-Chen;Chen, Chiung-Nien;Wu, Vin-Cent;Chuang, Li-Ying;Hsieh, Fon-Jou;Wu, C. H. Herbert;Tsai-Wu, Jyy-Jih
    • BMB Reports
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    • v.41 no.10
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    • pp.716-721
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    • 2008
  • To explore the effects of deregulated expression of the EBNA1 binding protein 2 (EBP2) on cell growth, we generated human HEK293 stable clones constitutively expressing an EBP2-EGFP fusion protein. We found both RNA and protein levels of cyclin E1, a dominant oncoprotein, were elevated in the EBP2- EGFP stable clones. These findings were confirmed by flow cytometry bivariate analysis of cyclin expression versus DNA content. Moreover, the increase in p21 expression and the specific phosphorylation at Ser1981 of ATM and Ser15 of p53 were also observed in these stable clones, and these observations may explain the failure to observe an increase in Cdk2 kinase activity. In addition, after one year of passage culture, the EBP2-EGFP stable clones tended to lose 4 to 5 chromosomes per cell when compared to that of control cells. All of these findings provide a possible link between deregulated expression of EBP2 and tumor development.

Evidence based practice within the complementary medicine context

  • McLean, Lisa;Micalos, Peter Steve;McClean, Rhett;Pak, Sok Cheon
    • CELLMED
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    • v.6 no.3
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    • pp.15.1-15.4
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    • 2016
  • Evidence based practice (EBP) is a system of applying the most current and valid high quality evidence to support clinical decision making in a healthcare setting. In the twenty five years since its inception, EBP has become the accepted benchmark for excellence in healthcare. Although the system emerged within the biomedical sciences, in the years since EBP has become normative across all healthcare modalities from dentistry, allied health to complementary and alternative medicine (CAM). Practicing evidence based medicine within any modality potentially offers the patient the best available care based on high quality evidence. Yet it is the nature of the evidence that provokes some questions about the suitability of EBP across all modalities of healthcare. The meta analysis of randomized controlled trial (RCT) stands at the pinnacle of the hierarchy of evidence in EBP. This forms a challenge to CAM due to the difficulty in reducing the elementals of a holistic naturopathic assessment of a patient into an answerable question to be tested within a RCT. On one level this makes EBP paradigmatically incompatible with CAM, yet on another level it presents the opportunity to redefine the parameters of what is considered high level evidence. EBP has become a tool, and at times a weapon wielded by governments and health insurance companies to direct healthcare funding and policy. The implications of the nature of accepted evidence are becoming far reaching. The pursuit of the best available healthcare for each individual is the focus of EBP. However, the injudicious use of this system to direct health policy is fraught with biomedical bias and dominance. This issue raises the challenge to CAM to present high level evidence according to the rules of evidence, or face the annihilation of centuries of empirical knowledge.

Identification of a Novel SNP Associated with Meat Quality in C/EBP${\alpha}$ Gene of Korean Cattle

  • Shin, S.C.;Kang, M.J.;Chung, E.R.
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.4
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    • pp.466-470
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    • 2007
  • CCAAT/enhancer binding protein ${\alpha}$($C/EBP{\alpha}$) plays an important role in lipid deposition and adipocyte differentiation. In order to find genetic markers to improve the meat quality of Korean cattle, the bovine $C/EBP{\alpha}$ gene was chosen as a candidate gene to investigate its association with carcass and meat quality traits in Korean cattle. A single nucleotide polymorphism (SNP) was identified at position 271 (A/C substitution) of coding region in the $C/EBP{\alpha}$ gene. A PCR-RFLP procedure with restriction enzyme SmaI was developed for determining the marker genotypes. The frequencies of alleles C and A and were 0.374 and 0.626, respectively. The genotype frequencies for CC, AC and AA were 12.9, 49.0 and 38.1%, respectively, in Korean cattle population. The frequencies of genotype were in agreement with Hardy-Weinberg equilibrium. Association analysis indicated that the gene-specific SNP marker of $C/EBP{\alpha}$ showed a significant association with marbling score (p<0.05). The animals with AA genotype had higher marbling score than those with the AC or CC genotype. Although further studies are needed to validate our results, the $C/EBP{\alpha}$ gene could be useful as a genetic marker for carcass and meat quality traits in Korean cattle.

Anti-Obesity Effect of Ethyl Acetate Extracts from Agrimonia pilosa Ledeb. in 3T3-L1 Preadipocytes (3T3-L1 지방전구세포에서 용아초 에틸아세테이트 추출물의 항비만 효과)

  • Lee, Jung-A;Ahn, Eun-Kyung;Hong, Seong-Su;Oh, Joa-Sub
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.2
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    • pp.161-167
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    • 2012
  • To evaluate the anti-obesity effect of Agrimonia pilosa L., this study investigated that ethyl acetate extract from A. pilosa L. (EAAP) suppresses lipid accumulation and inhibits expression of adipogenic marker genes, such as peroxisome proliferator activated receptor ${\gamma}$ (PPAR${\gamma}$), CCAAT-enhancer-binding protein ${\alpha}$ (C/EBP${\alpha}$), glucose transporter 4 (GLUT4), and adiponectin in 3T3-L1 preadipocytes. We demonstrated that EAAP inhibited adipocyte differentiation and expression of PPAR${\gamma}$ and C/EBP${\alpha}$ mRNA levels in a dose-dependent manner. In addition, EAAP reduced the PPAR${\gamma}$ transcriptional activity stimulated by rosiglitazone in HEK 293T cells and decreased the expression of GLUT4 and adiponectin in 3T3-L1 cells. These results suggest that EAAP inhibits preadipocyte differentiation and adipogenesis by blocking of PPAR${\gamma}$ and C/EBP${\alpha}$ gene expression in 3T3-L1 cells.