• 제목/요약/키워드: E4

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Clast4의 과발현에 의한 세포 증식의 감소 (Overexpression of Clast4 Reduces Cell Proliferation)

  • 강민국;한승진
    • 생명과학회지
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    • 제24권10호
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    • pp.1144-1150
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    • 2014
  • eIF4E는 번역개시과정에서 중심조절자 역할을 한다. eIF4E와 eIF4G의 결합이 mRNA의 번역을 촉발하기 때문에, 여러 단백질들이 이 결합을 저해함으로써 번역과정을 조절한다. 인간 4E-T는 eIF4E 결합단백질 중의 하나로, 결합한 mRNA의 번역을 저해할 뿐 아니라, eIF4E를 processing body (P-body)로 이동시키는 기능을 가지고 있다. Clast4는 인간의 4E-T와 상동성을 가지는 생쥐 단백질로 번역 조절에 중요한 기능을 할 것으로 추측되지만, 그 특징은 아직 잘 알려져 있지 않다. 본 연구에서는 Clast4의 인산화된 상태와 eIF4E와의 결합력, Clast4 과발현시 세포증식의 변화에 대한 특징을 관찰하였다. Clast4는 PKA에 의해 in vivo에서 아미노말단의 몇몇 잔기가 인산화되는 것으로 확인되었다. 그러나 PKA에 의해 인산화된 Clast4는 eIF4E와의 결합력이나 Clast4의 세포 내 위치에는 큰 변화가 없었다. Clast4는 eIF4E1과 CPEB와 결합하며, Clast4의 보존된 eIF4E 결합 서열인 $YXXXXL_{\phi}$가 eIF4E1A와의 결합에서는 중요하지만 eIF4E1B와의 결합에서는 큰 영향이 없는 것으로 관찰되었다. 잘 알려져 있는 eIF4E 조절자인 4E-BP의 경우와 유사하게 Clast4를 과발현하였을 때 세포의 증식이 감소되었다. 이러한 결과는 Clast4가 세포 내에서 전반적인 번역 조절에 관여하고 있다는 것을 시사한다.

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

  • 박재완;문일수
    • 생명과학회지
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    • 제23권7호
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    • pp.941-946
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    • 2013
  • 신경세포의 가지돌기 내 단백질합성은 필요한 단백질을 실시간으로 제공할 수 있는 이점을 제공한다. 본 연구에서는 단백질합성인자 eIF4E와 그 억제 단백질인 eIF4EBP1의 발생단계별 표현을 배양한 해마신경세포를 면역 염색하여 조사하였다. eIF4E는 가지돌기에 점박이 모양으로 표현되었으며, 핵에는 표현되지 않았다. 그러나 eIF4EBP1는 가지돌기 뿐 아니라 발생초기(DIV 0.5)부터 핵에서 표현되었으며 성숙한 세포에서 핵에 더욱 뚜렷이 표현되었다. eIF4E 혹은 eIF4EBP1의 PSD95과의 colocalization은 $39.1{\pm}9.6%$$70.5{\pm}5.2%$ (DIV 7), $57.7{\pm}8.2%$$36.0{\pm}3.1%$ (DIV 10), $29.9{\pm}2.9%$$40.2{\pm}11.7%$ (DIV 20)이었다. eIF4E와 eIF4EBP1의 colocalizatin은 $18.5{\pm}2.6%$ (DIV 7), $11.1{\pm}3.9%$ (DIV 10), $38.6{\pm}5.6%$ (DIV 20)이었다. 이 결과는 eIF4E 및 eIF4EBP1의 많은 부분이 연접후에 위치하며, 발생초기에는 eIF4E가 활동적인 형태로 존재하지만, 성숙 신경세포에서는 eIF4EBP1과 결합하여 비활성적인 형태로 존재함을 의미한다.

Translation Initiation Factor 4E (eIF4E) is Regulated by Cell Death Inhibitor, Diap1

  • Lee, Sun Kyung;Lee, Ji Sun;Shin, Ki Soon;Yoo, Soon Ji
    • Molecules and Cells
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    • 제24권3호
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    • pp.445-451
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    • 2007
  • Translation initiation factor 4E (eIF4E) is a key regulator of protein synthesis. Abnormal regulation of eIF4E is closely linked to oncogenic transformation. Several regulatory mechanisms affecting eIF4E are discussed, including transcriptional regulation, phosphorylation and binding of an inhibitor protein. However it is not clear how the level of eIF4E protein is regulated under basal conditions. Here we demonstrate that Diap1 (Drosophila Inhibitor of Apoptosis Protein), a cell death inhibitor, binds directly to eIF4E and poly-ubiquitinates it via its E3 ligase activity, promoting its proteasome-dependent degradation. Expression of Diap1 caused a reduction of Cyclin D1 protein level and inhibited the growth stimulation induced by overexpression of eIF4E. Taken together, our results suggest that the level of eIF4E protein is regulated by Diap1, and that IAPs may play a role in cap-dependent translation by regulating the level of eIF4E protein.

Studies on the Distribution of Plasma Lipid Profiles and Body Fatness According to Apo E Polymorphism in Normolipidemic Korean Women

  • Lee, Myoung-Sook
    • Preventive Nutrition and Food Science
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    • 제2권4호
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    • pp.338-347
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    • 1997
  • Apo E polymorphism(e2, e3, e4) was among the first reported genetic polymorphism that explained part of the normal vairation in plasma cholesterol concentrations. Both alleles E2 and E4 are significantly more frequent in patients with mixed forms of hyperlipidemia and contribute on the observed differences in CHD risk among different populations. Effects of apo E polymorphism on the distribution of plasma lipid profiles were studied in 89 normolipidemic healthy females, aged 19 up to 22 years. The relative frequencies of E3/3 was 0.787, E3/2 was 0.101, E3/4 allele was 0.112 and no E2/2, E2/4 and E4/4 were found. Weight, height and %LBM were elevated in E2 than those in E3&E4. No differences in the blood pressure among apo E isomers were found, otherwise the pulsation was higher in E4 than that in the others. There were no differences in plasma total-, total DL-, HDL$_3$-, HDL$_2$ cholesterol, apo B-100 and apo A-I, However, phenotype means rank E3/2>E3/3>E3/4 in average TG levels(p<0.0001) significantly, and rank E3/4>E3/3>E3/2 in LDL cholesterol levels. These results were related to the correlation between atherogenic indiced (AI) such as LDL/HDL, (TC-HDL)/HDL, HDL$_3$/HDL$_2$. The ratio of HDL$_3$& HDL$_2$was significantly increased in E2 & E4 than that in E3(P=0.043). LCAT activity was not different between E2 and E3 but was highly increased in E4 (p<0.0001 among apo E isomers), but CETP was not different. Since the negative correlation between LCAT and CETP in apo E2(r=-0.491) was stronger than that in apo E3, E2 allele impacts the clearance of plasma apo E mediated lipoproteins. In conclusion firstly, E4 mediated alteration through LDL or E receptors results in lower TG or higher $\beta$-lipoprotein levels and E2 shows reciprocal effects of E4, respectively. Second, E4 allele was more atherogenic than E2 allele because the higher levels of AI such as HDL$_3$/HDL$_2$ were criticized.

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Apo E 유전자 변이형이 혈청지질 및 유리아미노산 농도에 미치는 영향 (Effects of Apo E Polymorphism on the Plasma Lipid Profiles and Free Amino Acids in Korean Women)

  • 이명숙;박태선
    • 한국식품영양과학회지
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    • 제28권1호
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    • pp.225-232
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    • 1999
  • Apo E polymorphism(e2, e3, e4) was among the first reported genetic polymorphism that explained part of the normal variation in plasma cholesterol concentrations. Among 62 normolipidemic healthy females, aged 19 up to 22 years, the relative frequencies of E3/3 was 0.806(n=50), E3/2 was 0.081(n=5), E3/4 allele was 0.113(n=7), and no E2/2, E2/4 and E4/4 were found. Based on the five samples of E2 allele, five subjects were randomly selected by E3 and E4 groups for the study of effects of apo E polymorphism on the distribution of serum lipid and amino acids profiles. No differences in the anthro pometric data among apo E isomers were found, otherwise the pulsation was higher in E4 than that in the others. There were no differences in plasma total HDL , HDL3 , HDL2 & LDL cholesterol, and apo A I concentrations. However, phenotype means significantly rank E2>E3>E4 allele in average TG levels(p=0.014), and rank E4>E3>E2 in total cholesterol levels(p=0.011). Atherogenic index(AI) such as lipoproteins was significantly increased in E2 & E4 than that in E3(p=0.045). Subjects with E3/2 allele had significantly higher concentrations of glutamine, phosphoserine and taurine, while subjects with E3/4 allele showed significantly lower concentrations of arginine and am inobutyrate and elevated level of phosphoserine in plasma com pared to those of E3/3 allele. Higher level of plasma taurine in subjects with E3/2 or E3/4 allele appears to be related to the elevated level of plasma total and LDL cholesterol concentrations compared to those of E3/3 allele.

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아포리포 단백질 E 유전자의 E2와 E4 변이형이 정상 한국여성의 혈중 지질 수준 분포에 미치는 영향 (Apolipoprotein E2 & E4 Alleles Influence on the Distribution of the Human Plasma Lipid Profiles in Mormolipidemic Korean Women)

  • 이명숙
    • Journal of Nutrition and Health
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    • 제29권6호
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    • pp.642-650
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    • 1996
  • ApoE 유전자의 다형성은 인체 혈중 콜레스테롤 농도의 정상분포를 설명하는 중요한 인자이다. 특히, E2 와 E4 allele들은 고지혈증환자의 혈중에 현저히 나타나며, 각 다른 인종간의 이틀의 상대빈도수가 관상 동맥 질환 유발 위험도와의 상관관계가 아주 높다. Apo E 유전자의 다형성이 혈중 지질 대사변화 에 미치는 영향에 관한 실험은 105명의 건강한 한국여성을 대상으로 시행되었다. Apo E alleles의 한국 인 상대빈도수는 E3가 0.848, E4가 0.087, 그리고 E2는 0.067이었다. 본 연구에서는 E2/2 표현형이 나 타나지 않았지만, 중국 및 일본인과 같이 E4와 E2 allele가 아주 낮았다 최고및 최저혈압, 맥박(p

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Double Mutations in eIF4E and eIFiso4E Confer Recessive Resistance to Chilli Veinal Mottle Virus in Pepper

  • Hwang, JeeNa;Li, Jinjie;Liu, Wing-Yee;An, Song-Ji;Cho, Hwajin;Her, Nam Han;Yeam, Inhwa;Kim, Dosun;Kang, Byoung-Cheorl
    • Molecules and Cells
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    • 제27권3호
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    • pp.329-336
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    • 2009
  • To evaluate the involvement of translation initiation factors eIF4E and eIFiso4E in Chilli veinal mottle virus (ChiVMV) infection in pepper, we conducted a genetic analysis using a segregating population derived from a cross between Capsicum annuum 'Dempsey' containing an elF4E mutation ($pvr1^2$) and C. annuum 'Perennial' containing an elFiso4E mutation (pvr6). C. annuum 'Dempsey' was susceptible and C. annuum 'Perennial' was resistant to ChiVMV. All $F_1$ plants showed resistance, and $F_2$ individuals segregated in a resistant-susceptible ratio of 166:21, indicating that many resistance loci were involved. Seventy-five $F_2$ and 329 $F_3$ plants of 17 families were genotyped with $pvr1^2$ and pvr6 allele-specific markers, and the genotype data were compared with observed resistance to viral infection. All plants containing homozygous genotypes of both $pvr1^2$ and pvr6 were resistant to ChiVMV, demonstrating that simultaneous mutations in elF4E and eIFiso4E confer resistance to ChiVMV in pepper. Genotype analysis of $F_2$ plants revealed that all plants containing homozygous genotypes of both $pvr1^2$ and pvr6 showed resistance to ChiVMV. In protein-protein interaction experiments, ChiVMV viral genome-linked protein (VPg) interacted with both eIF4E and eIFiso4E. Silencing of elF4E and eIFiso4E in the VIGS experiment showed reduction in ChiVMV accumulation. These results demonstrated that ChiVMV can use both eIF4E and eIFiso4E for replication, making simultaneous mutations in eIF4E and eIFiso4E necessary to prevent ChiVMV infection in pepper.

식이성 비타민 E가 사염화탄소를 투여한 흰쥐의 체내지질성분에 미치는 영향 (Effect of Dietary Vitamin E on the Lipid Composition of Rats Treated with Carbon Tetrachloride)

  • 송가현;조수열;박미리
    • 한국식품영양과학회지
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    • 제19권4호
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    • pp.279-284
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    • 1990
  • This experiment was conducted to study the effect of dietary vitamin E on the lipid composi-tion of rats treated with carbon tetrachloride. Rats were divided into five groups I. e. C(soybean oil with vitamin E(40mg/kg diet)) EF(CCl4 with vitamin E deficient diet) 40E(CCl4 with vitamin E(40mg/kg diet) 400E(CCl4 with vitamin E(400mg/kg diet) 800E(CCl4 with vitamin E(800mg/kg diet) Body weight gain and food efficient ratio were not observed significant differences. The liver weight was significantly increased in the CCl4 treated groups but the liver weight of 800E group was significantly lower than that of EF group. In EF and 40E groups kidney weights were significantly higher compared to that of C group. The content of total lipid in liver of 40E and 400E groups were significantly higher than that of control group but in 400E and 800E groups the contents were significantly lower compared with that of EF group. The content of triglyceride in liver was significantly higher in the CCl4 treated group and the content of cholesterol was significantly higher in the EF and 40E groups but those of 800E group were significantly lower compared with those of EF group. In CCl4 administration groups were significantly higher than those of control group and 400E and 800E groups were significantly lower than those of EF group.

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핸드스프링 몸접어 앞공중돌기동작의 운동학적 분석 (The Kinematic Analysis of Handspring Salto Forward Piked)

  • 권오석
    • 한국운동역학회지
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    • 제17권1호
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    • pp.145-153
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    • 2007
  • The purpose of this study is to compare and analyze the phase-by-phase elapsed time, the COG, the body joint angle changes and the angular velocities of each phase of Handspring Salto Forward Piked performed by 4 college gymnasts through 3D movement analysis program. 1. The average elapsed time for each phase was .13sec for Phase 1, .18sec for Phase 2, .4sec for Phase 3, and .3sec for Phase 5. The elapsed time for Phase 1 to Phase 3 handspring was .35sec on average and the elapsed time for Phase 4 to Phase 5 handspring salto forward piked was .7sec on average. And so it showed that the whole elapsed time was 1.44sec. 2. The average horizontal changes of COG were 93.2 cm at E1, 138. 5 cm at E2, 215.7 cm at E3, 369.2 cm at E4, 450.7 cm at E5, and 553.1 cm at E6. The average vertical changes of COG were 83.1 cm at E1, 71.3 cm at E2, 78.9 cm at E3, 93.7 cm at E4, 150.8 cm at E5, and 97.2 cm at E6. 3. The average shoulder joint angles at each phase were 131.6 deg at E1, 153.5 deg at E2, 135.4 deg at E3, 113.4 deg at E4, 39.6 deg at E5, and 67.5 deg at E6. And the average hip joint angles at each phase were 82.2 deg at E1, 60 deg at E2, 101.9 deg at E3, 161.2 deg at E4, 97.7 deg at E5, and 167 deg at E6. 4. The average shoulder joint angular velocities at each phase were 130.9deg/s E1, 73.1 deg/s at E2, -133.9 deg/s at E3, -194.4 deg/s at E4, 29.4 deg/s at E5, and -50.1 deg/s at E6. And the average hip joint angular velocities at each phase were -154.7 deg/s E1, -96.5 deg/s at E2, 495.9 deg/s at E3, 281.5 deg/s at E4, 90.3 deg/s at E5, and 181.7 deg/s at E6. The results shows that, as for the performance of handspring salto forward piked, it is important to move in short time and horizontally from the hop step to the point to place the hands on the floor and jump, and to stretch the hip joints as much as possible after the displacement of the hands and to keep the hip joints stretched and high in the vertical position at the takeoff. And it is also important to bend the shoulder joints and the hip joints fast and spin as much as possible after the takeoff, and to decrease the speed of spinning by bending he shoulder joints and the hip joints quickly after the highest point of COG and make a stable landing.

Apolipoprotein E Polymorphism in the Korean Population

  • Eom Yong-Bin;Jo Yoon-Kyung;Lee Duk-Chul;Im Jee-Aee
    • 대한의생명과학회지
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    • 제11권4호
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    • pp.429-434
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    • 2005
  • Apolipoprotein E (apoE) restriction isotyping used oligonucleotides to amplify apoE gene sequences containing amino acid positions 112 and 158. The amplification products were digested with HhaI and subjected to electrophoresis on $4\%$ agarose gel. Each of the isoforms was distinguished by a unique combination of HhaI fragment sizes that enabled unambiguous typing of all homozygotic and heterozygotic combinations. HhaI cleaves at GCGC encoding 112arg (E4) and 158arg (E3, E4), but does not cut at GTGC encoding 112cys (E2, E3) and] 58cys (E2). DNA was isolated from 72 study participants and apoE genotypes were determined utilizing the polymerase chain reaction and restriction isotyping. In the entire group of subjects, $38 (52.8\%)$ had apo E4/4 or E3/4 (Group E4), $28(38.9\%)$ had the apo E3/3 genotype (Group E3) and $6(8.3\%)$ had apo E2/2 or E2/3 (Group E2). This genotypic information may help to identify individuals at increased risk for several diseases.

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