• Journal of Life Science
• /
• v.24 no.10
• /
• pp.1144-1150
• /
• 2014

The eIF4E protein is the key regulator of translation initiation. The interaction of eIF4E with eIF4G triggers the translation of mRNA, and several proteins interrupt this association to modulate translation. Human 4E-T is one of the eIF4E-binding partners that represses the translation of bound mRNAs, and it is involved in the transport of eIF4E to processing bodies (P-bodies). Although Clast4, the mouse homolog of human 4E-T, might play critical roles in the regulation of translation, its properties are not well known. In this report, we deciphered the properties of Clast4 by determining its phosphorylation state, binding to eIF4E, and effects of overexpression on cell proliferation. Clast4 was phosphorylated by protein kinase A (PKA) in vivo on several residues of its amino terminus. Nevertheless, the PKA phosphorylation of Clast4 appeared to have no effect on either its eIF4E-binding ability or localization. Clast4 interacted with eIF4E1 and CPEB. The conserved eIF4E-binding sequence in Clast4, $YXXXXL_{\phi}$, was important for binding eIF4E1A but not eIF4E1B. Similar to that of another well-known eIF4E regulator, the eIF4E binding protein (4E-BP), the overexpression of Clast4 decreased cell proliferation. These results suggest that Clast4 acts as a global translation regulator in cells.

• Journal of Life Science
• /
• v.23 no.7
• /
• pp.941-946
• /
• 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.

• Molecules and Cells
• /
• v.24 no.3
• /
• pp.445-451
• /
• 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.

• Preventive Nutrition and Food Science
• /
• v.2 no.4
• /
• pp.338-347
• /
• 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.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.28 no.1
• /
• pp.225-232
• /
• 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.

• Journal of Nutrition and Health
• /
• v.29 no.6
• /
• pp.642-650
• /
• 1996

Apo E polymorphism (e2, e3, e4) was among the first reported genetic polymorphism that explained part of the normal variation 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 105 normolipidemic healthy women. The relative frequencies of common alleles for gene locus of apo E in this study were that E3 allele was 0.848, E4 allels was 0.087, and E2 allele was 0.067. SBP and DBP were slightly more elevated in E2 allele than those in E3 and E4. The pulsation was also significantly (p<0.016) increased by E2 allele with excess body fat % in E2 allele. There were no differences in total-, total HDL-, VLDL+LDL-, VLDL- and LDL cholesterol among the apo E alleles. However, apo E2 allele subject had lower level of total HDL and HDL2 cholesterol (P<0.047) and significantly higher lev디 of HDL3 cholesterol (P<0.05) than those in apo E3 and E4 allele subject. The conclusion is that first, it seems that apo E4-mediated alteration through LDL B/E receptors or E receptors in cholesterol metabolism results in lower plasma TG or remanate particles and in higher levels of VLDL+LDL or LDL. Second, apo E2 allele shows reciprocal effects of E4 on the plasma lipid metabolism, respecitvely. Third, apo E2 allele was more atherogenic than apo E4 because the higher levels of HDL3/HDL2 ratio and atherogenic index[(TC-HDL)/HDL]were criticized.

• Molecules and Cells
• /
• v.27 no.3
• /
• pp.329-336
• /
• 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.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.19 no.4
• /
• pp.279-284
• /
• 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.

• Korean Journal of Applied Biomechanics
• /
• v.17 no.1
• /
• pp.145-153
• /
• 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.

• Biomedical Science Letters
• /
• v.11 no.4
• /
• pp.429-434
• /
• 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.