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Eukaryotic initiation factor 5A2 and human digestive system neoplasms 被引量:3
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作者 Qing-Bin Meng Jing-Jing Peng +3 位作者 Zi-Wei Qu Xiao-Min Zhu Zhang Wen Wei-Ming Kang 《World Journal of Gastrointestinal Oncology》 SCIE CAS 2019年第6期449-458,共10页
Eukaryotic initiation factor 5A2(eIF5A2),as one of the two isoforms in the family,is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer.Overexpression or gene a... Eukaryotic initiation factor 5A2(eIF5A2),as one of the two isoforms in the family,is reported to be a novel oncogenic protein that is involved in multiple aspects of many types of human cancer.Overexpression or gene amplification of EIF5A2 has been demonstrated in many cancers.Accumulated evidence shows that eIF5A2 initiates tumor formation,enhances cancer cell growth,increases cancer cell metastasis,and promotes treatment resistance through multiple means,including inducing epithelial–mesenchymal transition,cytoskeletal rearrangement,angiogenesis,and metabolic reprogramming.Expression of eIF5A2 in cancer correlates with poor survival,advanced disease stage,as well as metastasis,suggesting that eIF5A2 function is crucial for tumor development and maintenance but not for normal tissue homeostasis.All these studies suggest that eIF5A2 is a useful biomarker in the prediction of cancer prognosis and serves as an anticancer molecular target.This review focuses on the expression,subcellular localization,post-translational modifications,and regulatory networks of eIF5A2,as well as its biochemical functions and evolving clinical applications in cancer,especially in human digestive system neoplasms. 展开更多
关键词 eukaryotic translation initiation factor 5A2 HYPUSINE MODIFICATION ACETYLATION MODIFICATION Drug resistance Cancer THERAPEUTICS
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Localization and function of a eukaryotic-initiation-factor-2-associated 67-kDa glycoprotein
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作者 Shiyong Wu,Edison Biotechnology Institute,Department of Chemistry and Biochemistry,Ohio University,Athens,OH 45701,United States 《World Journal of Biological Chemistry》 CAS 2010年第10期313-320,共8页
AIM: To study the localization and function of a eukaryotic initiation factor 2 (eIF2α)-associated 67-kDa glycoprotein (p67).METHODS: Immunofluorescence staining,35S-Met/Cys metabolic labeling,Western blotting analys... AIM: To study the localization and function of a eukaryotic initiation factor 2 (eIF2α)-associated 67-kDa glycoprotein (p67).METHODS: Immunofluorescence staining,35S-Met/Cys metabolic labeling,Western blotting analysis,sucrose gradient centrifugation and high speed centrifugation were used to determine the localization of proteins in transiently transfected COS-1 cells.Transient co-transfection followed by co-immunoprecipitation was used to study the interaction between p67 and double-stranded RNA (dsRNA)-dependent protein kinase (PKR).Wheat germ agglutinin agarose beads were used to absorb glycosylated proteins.In vivo 32P-labeling followed by immunoprecipitation and Western blotting were used to measure PKR autophosphorylation,eIF2α phosphorylation,and p67 expression in normal and breast cancer cells.RESULTS: The image from immunofluorescence staining showed that p67 was overexpressed in the cytosol but not in the nucleus.In a sucrose gradient,approxi-mately 30% of the overexpressed p67 was bound with ribosomes.p67 interacted with the kinase domain,butnot the dsRNA-binding domains of PKR.Only the glycosylated p67 was associated with the ribosome,and p67 did not compete with PKR for ribosome binding.In breast cancer cells,there was increased autophosphorylation of PKR but no phosphorylation of eIF2α,compared with normal breast cells.α The ratio of glycosylated/deglycosylated p67 was altered in breast cancer cells.CONCLUSION: Glycosylation of p67 is required for its ribosomal association and can potentially inhibit PKR via interaction with the kinase domain of PKR. 展开更多
关键词 eukaryotic translation initiation factor 2 p67 DOUBLE-STRANDED RNA dependent protein KINASE PHOSPHORYLATION Cancer
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Relationship between Eukaryotic Translation Initiation Factor 4E and Malignant Angiogenesis in Non-Hodgkin Lymphoma 被引量:1
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作者 赵艳霞 刘文励 +2 位作者 周晟 周剑锋 孙汉英 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2005年第6期636-638,654,共4页
The relationship between angiogenesis and eukaryotic translation initiation factor 4E (EIF4E) expression level in non Hodgkin lymphoma (NHL) was studied. Mean microvessel density (MVD) and EIF4E were detected in... The relationship between angiogenesis and eukaryotic translation initiation factor 4E (EIF4E) expression level in non Hodgkin lymphoma (NHL) was studied. Mean microvessel density (MVD) and EIF4E were detected in 52 lymph node samples paraffin sections of patients with newly diagnosed NHL by the way of immunohistochemistry. Antisense EIF4E cDNA was cloned into plasmid pcDNA3.1 (+) and transfected into Raji cells. A series of angiogenesis related factors,including vascular endothelial growth factor (VEGF), matrix metalloproteinases 9 (MMP-9) and tissue inhibitor of metalloproteinases-2 (TIMP-2) proteins were detected by Western blot. The results showed that: (1) The Expression of EIF4E and MVD was higher in aggressive lymphomas than in indolent lymphomas(P〈0.05)and the expression of EIF4E was positively correlated with MVD in lymph node of NHL(r=0. 695, P〈0.01). (2) Antisense EIF4E eukaryocytic expression vector (pcDNA3. 1-EIF4Eas) was constructed successfully. (3) EIF4E, VEGF and MMP-9 were expressed at high levels in Raji cells as compared to normal human peripheral blood monocular cells (NHPMC), and blockage of EIF4E expression brought down the expression of VEGF and MMP-9. However, TIMP-2 was undetectable in Rail cells, although a moderate level of TIMP-2 was detected in NHPMC. It was concluded that the increased EIF4E expression was associated with aggressive property of NHL. 展开更多
关键词 eukaryotic translation initiation factor 4E non-Hodgkin lymphoma matrix metalloproteinases 9 tissue inhibitor of metalloproteinases-2
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Different Eukaryotic Initiation Factor 2Be Mutations Lead to Various Degrees of Intolerance to the Stress of Endoplasmic Reticulum in Oligodendrocytes 被引量:2
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作者 Na Chen Yu-Wu Jiang +5 位作者 Hong-Jun Hao Ting-Ting Ban Kai Gao Zhong-Bin Zhang Jing-Min Wang Ye Wu 《Chinese Medical Journal》 SCIE CAS CSCD 2015年第13期1772-1777,共6页
Vanishing white matter disease (VWM), a human atitosomal recessive inherited leukoencephalopathy, is due to mutations in eukaryotic initiation factor 2B (elF2B). elF2B is responsible for tile initiation of protein... Vanishing white matter disease (VWM), a human atitosomal recessive inherited leukoencephalopathy, is due to mutations in eukaryotic initiation factor 2B (elF2B). elF2B is responsible for tile initiation of protein synthesis by its guanine nucleotide exchange lhctor (GEF) activity. Mutations ofelF2B impair GEF activity at different degree. Previous studies implied improperly activated unlblded protein response (UPR) and endoplasmic reticulum stress (ERS) participated in the pathogenesis ofVWM. Autophagy relieves endoplasmic reticulum load by eliminating the unfolded protein. It is still unknown the effects of genotypes on the pathogenesis. In this work, UPR and autophagy flux were analyzed with different mutational types. Methods: ERS tolerance, reflected by apoptosis and cell viability, was detected in human oligodendrocyte cell line transfected with the wild type, or different mutations of p. Argl 13 His, p. Arg269* or p. Ser610-Asp613del in el F2 Be. A representative U PR-PERK component of activating transcription lhctor 4 (ATF4) was measured under the basal condition and ERS induction. Autophagy was analyzed the flux in the presence of lysosomal inhibitors. Results: The degree of ERS tolerance varied in different genotypes. The truncated or deletion mutant showed prominent apoptosis cell viability declination after ERS induction. The most seriously damaged GEF activity ofp. Arg269* group underwent spontaneous apoptosis. The truncated or deletion mutant showed elevated ATF4 under basal as well as ERS condition. Decreased expression of LC3-1 and LC3-11 in the mutants reflected an impaired autophagy flux, which was more obvious in the truncated or deletion mutants alter ERS induction. Conclusions: GEF activities in dilt;erent genotypes could influence the cell ERS tolerance as well as compensatory pathways of UPR and autophagy. Oligodendrocytes with truncated or deletion inutants showed less tolerable to ERS. 展开更多
关键词 Autophagy Flux: EIF2B5 eukaryotic initiation factor 2Bε) Endoplasmic Reticulum Stress: Un|blded Protein P esponse:Vanishing White Matter Disease
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Crystal structure of the C-terminal domain of the ε subunit of human translation initiation factor eIF2B
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作者 Jia Wei Minze Jia +4 位作者 Cheng Zhang Mingzhu Wang Feng Gao Hang Xu Weimin Gong 《Protein & Cell》 SCIE CSCD 2010年第6期595-603,共9页
Eukaryotic translation initiation factor eIF2B,the guanine nucleotide exchange factor(GEF)for eIF2,catalyzes conversion of eIF2·GDP to eIF2·GTP.The eIF2B is composed of five subunits,α,β,γ,δandε,within ... Eukaryotic translation initiation factor eIF2B,the guanine nucleotide exchange factor(GEF)for eIF2,catalyzes conversion of eIF2·GDP to eIF2·GTP.The eIF2B is composed of five subunits,α,β,γ,δandε,within which theεsubunit is responsible for catalyzing the guanine exchange reaction.Here we present the crystal structure of the C-terminal domain of human eIF2Bε(eIF2Bε-CTD)at 2.0-Åresolution.The structure resembles a HEAT motif and three charge-rich areas on its surface can be identified.When compared to yeast eIF2Bε-CTD,one area involves highly conserved AA boxes while the other two are only partially conserved.In addition,the previously reported mutations in human eIF2Bε-CTD,which are related to the loss of the GEF activity and human VWM disease,have been discussed.Based on the structure,most of such mutations tend to destabilize the HEAT motif. 展开更多
关键词 eukaryotic translation initiation factor 2B(eIF2B) guanine nucleotide exchange factor(GEF) crystal structure HEAT motif vanishing white matter(VWM)
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声门上型喉鳞状细胞癌组织VEGF、MMP-2、eIF4E的表达及临床意义 被引量:4
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作者 孙树军 刘清明 +2 位作者 田军 周建明 张爱玲 《中国耳鼻咽喉颅底外科杂志》 CAS 2007年第5期332-336,共5页
目的研究声门上型喉鳞癌及癌旁组织中VEGF、MMP-2、eIF4E的表达及与临床病理参数的关系。方法采用免疫组化SP法检测28例声门上喉鳞癌组织及癌旁组织中VEGF、MMP-2、eIF4E的表达。结果在声门上型喉癌组织中VEGF、MMP-2、eIF4E阳性表达率... 目的研究声门上型喉鳞癌及癌旁组织中VEGF、MMP-2、eIF4E的表达及与临床病理参数的关系。方法采用免疫组化SP法检测28例声门上喉鳞癌组织及癌旁组织中VEGF、MMP-2、eIF4E的表达。结果在声门上型喉癌组织中VEGF、MMP-2、eIF4E阳性表达率分别为78.57%,75%,89.28%;在癌旁组织中阳性表达率分别为21.42%,17.85%,42.85%。三者在肿瘤组织及癌旁组织中的表达差异有统计学意义(P<0.05),其表达与肿瘤淋巴结转移密切相关(P<0.05),三者间存在正相关。结论VEGF、MMP-2、eIF4E是声门上喉鳞癌组织表达较敏感的标志物,可作为反应喉癌生物学行为的客观参考指标,有助于判断患者预后,及有利于肿瘤治疗方案的制定。 展开更多
关键词 喉肿瘤 鳞状细胞 血管内皮生长因子 基质金属蛋白酶-2 翻译起始因子-4E
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内质网应激蛋白激酶RNA样ER激酶(PERK)通路对肝星状细胞激活及Ⅰ型胶原蛋白表达的影响
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作者 黎凤炎 刘泽峰 +4 位作者 夏雨艳 王文娟 李琪 唐利瑕 张国 《临床肝胆病杂志》 CAS 北大核心 2024年第5期968-974,共7页
目的探讨内质网应激蛋白激酶RNA样ER激酶(PERK)/真核生物翻译起始因子2α(eIF2α)信号通路对肝星状细胞(HSC)活化的影响。方法收集11例肝穿刺病理提示S1~S4肝纤维化患者和9例肝血管瘤、肝腺瘤患者术后周围正常肝组织病理切片,进一步行... 目的探讨内质网应激蛋白激酶RNA样ER激酶(PERK)/真核生物翻译起始因子2α(eIF2α)信号通路对肝星状细胞(HSC)活化的影响。方法收集11例肝穿刺病理提示S1~S4肝纤维化患者和9例肝血管瘤、肝腺瘤患者术后周围正常肝组织病理切片,进一步行组织免疫组化检测PERK、eIF2α、C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(CHOP)表达情况;使用不同浓度的内质网应激诱导剂毒胡萝卜素(0、125、250、500、1000 nmol/L)作用于人HSC-LX2,使用qRT-PCR检测PERK mRNA及Western Blot检测PERK、肌醇需要酶1(IRE1)、激活转录因子6(ATF6)、CHOP及α平滑肌肌动蛋白(α-SMA)表达水平。使用慢病毒转染构建PERK稳定过表达LX-2组及对照组,并通过qRT-PCR检测PERK、eIF2α、α-SMA mRNA,Western Blot检测PERK、p-eIF2α、α-SMA蛋白表达,免疫荧光检测胶Ⅰ型原蛋白(COL1A1)表达。符合正态分布的计量资料两组间比较采用成组t检验,多组间比较采用单因素方差分析,进一步两两比较采用LSD-t检验;不符合正态分布的计数资料,两组间比较采用Mann-Whitney U秩和检验。结果与正常肝组织相比,肝纤维化患者肝组织中PERK、eIF2α及CHOP表达升高,差异均有统计学意义(Z=−3.56、t=−5.75、Z=−3.52,P值均<0.001)。不同浓度毒胡萝卜素作用后,与溶媒组相比,内质网相关蛋白PERK、CHOP、IRE1、ATF6及α-SMA蛋白表达显著升高(P值均<0.05)。与对照空载慢病毒组相比,PERK稳定过表达组PERK mRNA、eIF2αmRNA、α-SMA mRNA表达及PERK、p-eIF2α、α-SMA蛋白表达明显升高(P值均<0.05)。细胞免疫荧光结果提示,PERK过表达组COL1A1表达升高(P<0.05)。结论PERK过表达可诱导LX-2细胞α-SMA、胶原蛋白COL1A1表达,提示PERK信号通路可能是HSC活化的重要机制之一。 展开更多
关键词 内质网应激 真核细胞起始因子2 肝星状细胞 胶原Ⅰ型
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宫颈病变组织中PKR、p-PKR、p-EIF2α表达及意义 被引量:2
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作者 罗远材 瞿全新 糜若然 《天津医药》 CAS 北大核心 2010年第1期20-22,81,共4页
目的:探讨蛋白激酶R(PKR)→真核细胞翻译起始因子2α(EIF2α)信号传导通路中PKR、磷酸化型PKR、EIF2α(p-PKR、p-EIF2α)表达与宫颈病变的相关性、在宫颈肿瘤形成演进过程中的作用及对宫颈癌患者预后的影响。方法:采用免疫组化法检测PKR... 目的:探讨蛋白激酶R(PKR)→真核细胞翻译起始因子2α(EIF2α)信号传导通路中PKR、磷酸化型PKR、EIF2α(p-PKR、p-EIF2α)表达与宫颈病变的相关性、在宫颈肿瘤形成演进过程中的作用及对宫颈癌患者预后的影响。方法:采用免疫组化法检测PKR、p-PKR、p-EIF2α在63例宫颈癌、114例宫颈上皮内瘤样病变(CINⅠ~Ⅲ)、15例正常宫颈组织中的表达。结果:PKR在各组的阳性表达率随宫颈病变级别升高而升高,并与宫颈病变级别呈正相关(P<0.05);p-PKR、p-EIF2α在各组的阳性表达率随宫颈病变级别升高而先升高、后下降;在宫颈癌组,PKR的阳性表达率明显高于p-PKR(P<0.01);宫颈癌患者临床分期晚者病情进展快(P<0.01),p-PKR、p-EIF2α阴性表达者病情进展快(P<0.05)。结论:PKR的表达与宫颈病变级别相关;在宫颈高级别病变中存在PKR、EIF2α磷酸化障碍或p-PKR、p-EIF2α去磷酸化机制,使宫颈病变进展,可能导致宫颈癌患者预后不良。 展开更多
关键词 宫颈肿瘤 宫颈上皮内瘤样病变 蛋白激酶类 真核细胞起始因子2 免疫组织化学
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鸡真核生物翻译起始因子2α的原核表达与多克隆抗体的制备 被引量:1
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作者 袁晓琴 陈仕怡 +5 位作者 刘梦茜 李春燕 许丽惠 周五朵 吴异健 王全溪 《江西农业大学学报》 CAS CSCD 北大核心 2018年第1期151-156,共6页
为了获得鸡源真核生物翻译起始因子2α(Eukaryotic translation initiation factor alpha two,eIF2α)的多克隆抗体,首先经RT-PCR扩增了eIF2α基因的完整编码序列,并成功构建了重组表达质粒pET-32a(+)-eIF2α。将其转化BL21(DE3)经IPTG... 为了获得鸡源真核生物翻译起始因子2α(Eukaryotic translation initiation factor alpha two,eIF2α)的多克隆抗体,首先经RT-PCR扩增了eIF2α基因的完整编码序列,并成功构建了重组表达质粒pET-32a(+)-eIF2α。将其转化BL21(DE3)经IPTG诱导后,SDS-PAGE显示成功表达出分子量约51 ku的重组融合蛋白。该融合蛋白表达时的最佳诱导时间、诱导温度和IPTG浓度分别为10 h、45℃和1.5 mmoL/L。通过对该蛋白进行Ni^(2+)柱亲和层析纯化,得到了较高纯度的重组蛋白。将纯化后的eIF2α蛋白免疫新西兰黄兔,制备的多克隆抗体ELISA效价达1∶8 000,试验结果为后续eIF2α蛋白功能的研究提供了帮助。 展开更多
关键词 鸡真核生物翻译起始因子2α 原核表达 多克隆抗体
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猪EIF2S3基因克隆测序及其组织表达谱分析 被引量:1
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作者 龙熙 张廷焕 +5 位作者 赵久刚 蓝静 柴捷 郭宗义 王金勇 张亮 《南方农业学报》 CAS CSCD 北大核心 2018年第10期2062-2069,共8页
【目的】克隆猪EIF2S3基因mRNA全长,并进行生物信息学分析及检测其在猪各组织中的表达特征,为研究真核翻译起始因子2(eIF2)蛋白γ亚基的生物学功能打下基础。【方法】以荣昌猪胸腺mRNA为模板,采用RCAE-PCR克隆EIF2S3基因的m RNA全长序列... 【目的】克隆猪EIF2S3基因mRNA全长,并进行生物信息学分析及检测其在猪各组织中的表达特征,为研究真核翻译起始因子2(eIF2)蛋白γ亚基的生物学功能打下基础。【方法】以荣昌猪胸腺mRNA为模板,采用RCAE-PCR克隆EIF2S3基因的m RNA全长序列,在线完成各种生物信息学分析后,利用实时荧光定量PCR分析猪EIF2S3基因的组织表达特征。【结果】猪EIF2S3基因mRNA全长1813 bp,其中蛋白质编码区(CDS)长1419 bp,5'UTR区、3'UTR区分别长14和380 bp,编码472个氨基酸。EIF2S3蛋白分子量51.1 kD,理论等电点(pI)8.62,包含58个带正电的氨基酸和52个带负电的氨基酸,其前体蛋白靠近N端区域有一个强疏水区;EIF2S3蛋白的空间结构由α-螺旋、β-折叠、延伸及无规则卷曲构成。EIF2S3蛋白氨基酸序列与狗和大白鼠的相似性最高(99.6%),其次是马、猫、牛、羊和人类(99.4%),与斑马鱼的相似性最低(96.6%)。EIF2S3基因在猪的心脏、胸腺和淋巴组织中表达量较高,在脾脏和肌肉中呈中度表达,在肾脏中的表达量较低,而在肝脏中基本不表达。【结论】猪EIF2S3基因全长1813 bp,在核酸和氨基酸水平上与其他物种的EIF2S3基因高度同源,尤其与狗和大白鼠的遗传距离最近;其在猪心脏、胸腺和淋巴组织中的表达量较高,在肝脏中基本不表达,据此推测EIF2S3参与合成的蛋白更多地参与心脏泵血和免疫相关功能,基本不发挥能量代谢功能。 展开更多
关键词 真核翻译起始因子2(eIF2) EIF2S3基因 克隆 序列分析 组织表达谱
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siRNA沉默eIF4E诱导人喉癌Hep-2细胞凋亡及其机制 被引量:1
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作者 王贺彬 汪雅芳 +3 位作者 沈妙言 李娜 赵丽晶 滕博 《吉林大学学报(医学版)》 CAS CSCD 北大核心 2014年第1期39-43,I0001,共6页
目的:观察真核细胞翻译起始因子4E(eIF4E)基因的靶向小干扰RNA(siRNA)对喉癌Hep-2细胞中eIF4E基因表达的影响,探讨其诱导喉癌细胞凋亡的作用机制。方法:采用脂质体LipofectamineTM2000将siRNA-eIF4E转染入人喉癌Hep-2细胞(siRNA-eIF4E... 目的:观察真核细胞翻译起始因子4E(eIF4E)基因的靶向小干扰RNA(siRNA)对喉癌Hep-2细胞中eIF4E基因表达的影响,探讨其诱导喉癌细胞凋亡的作用机制。方法:采用脂质体LipofectamineTM2000将siRNA-eIF4E转染入人喉癌Hep-2细胞(siRNA-eIF4E组),同时设空白对照组和空质粒组。MTT法检测siRNA对Hep-2细胞增殖的抑制作用,罗丹明染色检测转染后细胞内线粒体膜电位的变化,TUNEL染色法检测细胞凋亡,RT-PCR和Western blotting法检测凋亡相关基因转录和蛋白表达水平的变化。结果:与空白对照组及空质粒组比较,siRNA-eIF4E组Hep-2细胞中eIF4E基因转录和表达水平明显下调(P<0.01),Hep-2细胞生存率下降(P<0.05),细胞线粒体膜电位降低(P<0.05),细胞凋亡率增加(P<0.05),凋亡相关基因Bim、Bid及Caspase-3表达上调(P<0.05)。结论:siRNA-eIF4E在体外可抑制人喉癌Hep-2细胞增殖,其机制可能是通过激活线粒体凋亡途径诱导Hep-2细胞凋亡。 展开更多
关键词 小干扰RNA 真核细胞翻译起始因子4E 喉肿瘤 HEP-2细胞 细胞凋亡
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日本血吸虫真核生物翻译起始因子2α亚基全长cDNA的克隆与功能分析 被引量:1
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作者 卢晓昭 彭鸿娟 陈晓光 《第一军医大学学报》 CSCD 北大核心 2003年第4期296-299,共4页
目的对用表达序列标签(EST)策略从日本血吸虫(Schistosomajaponicum)尾蚴cDNA文库中筛选出的新基因进行全长cDNA克隆及功能预测。方法将插入于pTriplEx2 质粒上的cDNA进行测序,测序结果经BLASTn程序搜索,发现该插入cDNA序列与曼氏血吸... 目的对用表达序列标签(EST)策略从日本血吸虫(Schistosomajaponicum)尾蚴cDNA文库中筛选出的新基因进行全长cDNA克隆及功能预测。方法将插入于pTriplEx2 质粒上的cDNA进行测序,测序结果经BLASTn程序搜索,发现该插入cDNA序列与曼氏血吸虫真核生物翻译起始因子2α亚基(eukaryotic translation initiation factor 2 alpha subunit, eIF2α) 基因高度同源。根据该EST序列设计与pTriplEx2 质粒上的5'端测序引物相匹配的PCR下游引物,从该cDNA文库中扩出包含eIF2α全长ORF的cDNA片段。将PCR产物纯化后克隆到pGEM-T载体上,并对此克隆进行测序得到其全长cDNA序列。用NCBI 站点的BLASTx及BLASTn程序对所获得的新基因序列进行同源性搜索;用blast two sequence程序对同源性高的基因进行核苷酸及氨基酸水平的同源性比较。同时用网上分析软件进行基序和保守区域的搜索。结果发现一个与曼氏血吸虫eIF2α亚基mRNA高度同源的日本血吸虫新基因,核苷酸与氨基酸水平的同一性分别为87%和79%,编码由327个氨基酸组成的蛋白序列。结论用EST策略筛选到一个日本血吸虫新基因,编码eIF2α亚基,全长编码序列与曼氏血吸虫eIF2α亚基mRNA高度同源。 展开更多
关键词 日本血吸虫 表达序列标签 基因克隆 真核生物翻译起始因子2α
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真核起始因子2α的磷酸化促进多柔比星介导的肝癌细胞凋亡 被引量:3
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作者 代荣阳 张艺 +3 位作者 陈绍坤 段春燕 刘友平 李洪 《泸州医学院学报》 2012年第4期349-352,共4页
目的:研究真核起始因子2α(eukaryotic initiation factor 2 alpha,eIF2α)的磷酸化对多柔比星诱导肝癌细胞凋亡的影响。方法:在采用eIF2α磷酸酶抑制剂salubrinal(抑制S51去磷酸化)和eIF2α突变载体eIF2αS51A(不能发生S51磷酸化)改变e... 目的:研究真核起始因子2α(eukaryotic initiation factor 2 alpha,eIF2α)的磷酸化对多柔比星诱导肝癌细胞凋亡的影响。方法:在采用eIF2α磷酸酶抑制剂salubrinal(抑制S51去磷酸化)和eIF2α突变载体eIF2αS51A(不能发生S51磷酸化)改变eIF2α磷酸化的基础上,利用流式细胞和免疫印迹技术分析eIF2α磷酸化对多柔比星诱导肝癌细胞LM3凋亡的影响。结果 :eIF2α突变载体eIF2αS51A抑制多柔比星介导的肝癌细胞LM3凋亡,而eIF2α磷酸酶抑制剂salubrinal则促进多柔比星介导的肝癌细胞LM3凋亡。结论:eIF2α的磷酸化在多柔比星介导的肝癌细胞凋亡中起重要作用。 展开更多
关键词 真核起始因子2α 多柔比星 凋亡 肝癌细胞
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EIF2AK3基因相关Wolcott-Rallison综合征1例并文献复习
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作者 张惠洁 王世彪 +3 位作者 郭晓峰 翁斌 林玲 郝燕 《中国当代儿科杂志》 CAS CSCD 北大核心 2019年第2期176-179,共4页
患儿,女,1个月29 d。因抽搐6 d、发现血糖增高5 d入院。血糖波动于正常或增高,糖化血红蛋白因过高无法检测,尿糖+~++++,空腹C肽0.19 ng/mL,胰岛素11.68μIU/mL。遗传性内分泌疾病基因Panel(检测基因412个,包含已知糖尿病相关基因49个)... 患儿,女,1个月29 d。因抽搐6 d、发现血糖增高5 d入院。血糖波动于正常或增高,糖化血红蛋白因过高无法检测,尿糖+~++++,空腹C肽0.19 ng/mL,胰岛素11.68μIU/mL。遗传性内分泌疾病基因Panel(检测基因412个,包含已知糖尿病相关基因49个)高通量测序发现患儿EIF2AK3基因存在新发c.2731_2732delAG和c.2980G>A复合杂合突变,均位于基因的激酶结构域。该婴儿被确诊为Wolcott-Rallison综合征(WRS)。WRS是一种罕见的常染色体隐性遗传疾病,以新生儿糖尿病、多发性骨骺发育不良和肝脏疾病为特征,新生儿糖尿病是WRS诊断的必备条件,EIF2AK3基因是WRS的致病基因。 展开更多
关键词 Wolcott-Rallison综合征 真核翻译始动因子2-α激酶3基因 新生儿糖尿病 基因检测
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CML细胞eIF4E和Trib2基因mRNA表达分析
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作者 黄莲芬 冯文莉 +1 位作者 万根平 罗红伟 《重庆医科大学学报》 CAS CSCD 北大核心 2010年第9期1358-1360,共3页
目的:为了探索慢性粒细胞白血病(Chronic myelogenous leukemia,CML)急变机理,寻求新的治疗靶标,我们对获得的9例CML病人骨髓标本以及CML急性红系变细胞株中K562细胞株中eIF4E基因和Trib2基因的表达水平进行初步检测,为进一步的研究奠... 目的:为了探索慢性粒细胞白血病(Chronic myelogenous leukemia,CML)急变机理,寻求新的治疗靶标,我们对获得的9例CML病人骨髓标本以及CML急性红系变细胞株中K562细胞株中eIF4E基因和Trib2基因的表达水平进行初步检测,为进一步的研究奠定基础。方法:分离骨髓单个核细胞,用Trizol裂解提取RNA,RT-PCR检测eIF4E基因和trib2基因mRNA的表达水平。结果:初步分析显示部分CML病人eIF4E基因mRNA表达水平很高,为CML疾病进展机制进一步研究奠定了基础。结论:部分CML病人骨髓标本中eIF4E和TRIB2基因mRNA表达水平较高,eIF4E和trib2有可能成为CML病人新的治疗靶点。 展开更多
关键词 慢性粒细胞白血病 真核细胞翻译起始因子4E Trib2
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Salubrinal通过eIF2α信号通路治疗非酒精性脂肪肝
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作者 张诗琪 刘大全 +1 位作者 李心乐 张平 《天津医药》 CAS 北大核心 2020年第5期375-380,共6页
目的探讨Salubrinal对肥胖诱导的非酒精性脂肪肝的疗效。方法选用30只雌性C57BL/6小鼠,随机分为对照(SCD)组、高脂饮食(HF)组和高脂饮食治疗(HF+S)组。HF组和HF+S组小鼠给予含脂量为60%的高脂饮食,4周肥胖诱导后,HF+S组接受Salubrinal... 目的探讨Salubrinal对肥胖诱导的非酒精性脂肪肝的疗效。方法选用30只雌性C57BL/6小鼠,随机分为对照(SCD)组、高脂饮食(HF)组和高脂饮食治疗(HF+S)组。HF组和HF+S组小鼠给予含脂量为60%的高脂饮食,4周肥胖诱导后,HF+S组接受Salubrinal皮下注射4周。实验过程中每周测量动物体成分变化,采取静脉血检测血脂指标,收集皮下、内脏脂肪和肝脏进行湿质量测定。为探索Salubrinal对肝脏的影响及作用机制,通过HE、油红O染色观察肝脏病理改变,Western blot检测肝组织e IF2α信号通路相关蛋白Bip、p-eIF2α、eIF2α、ATF4和CHOP的表达。结果与SCD组比较,HF组小鼠的血脂水平和脂肪堆积明显增加,Salubrinal治疗后,脂质紊乱情况减轻。同时,肝脏组织学检查显示,Salubrinal可以明显缓解肝脂肪变性严重程度并抑制异常脂质沉积。此外,Western blot分析表明,Salubrinal通过增加Bip、p-eIF2α/eIF2α和ATF4的表达量,降低CHOP的表达水平抑制内质网应激。结论Salubrinal能够有效缓解肥胖和肝脂肪变性,并通过eIF2α信号通路调控内质网应激而影响脂质代谢。 展开更多
关键词 非酒精性脂肪性肝病 肥胖症 内质网应激 真核细胞起始因子2 Salubrinal
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eIF5A-2下调对人肺癌细胞株A549DDP耐药及自噬的影响
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作者 李星 刘东升 杜钢 《西部医学》 2021年第4期493-497,共5页
目的探讨沉默真核翻译起始因子5A-2(eIF5A-2)对人肺癌细胞株A549/DDP耐药及自噬的影响。方法体外培养人肺癌细胞株A549、A549/DDP,转染细胞A549/DDP,细胞分为eIF5A-2-SiRNA组、阴性对照组(NC组)及空白对照组,另以A549细胞为正常对照组... 目的探讨沉默真核翻译起始因子5A-2(eIF5A-2)对人肺癌细胞株A549/DDP耐药及自噬的影响。方法体外培养人肺癌细胞株A549、A549/DDP,转染细胞A549/DDP,细胞分为eIF5A-2-SiRNA组、阴性对照组(NC组)及空白对照组,另以A549细胞为正常对照组。病毒感染72 h后,采用实时荧光定量PCR(qRT-PCR)检测细胞中eIF5A-2 mRNA表达水平,MTT法检测细胞DDP作用下A549/DDP细胞的耐药性,流式细胞术检测细胞的凋亡率,单酰戊二胺(MDC)染色检测细胞自噬水平,蛋白免疫印记(Western blot)法检测eIF5A-2、LC3Ⅱ及Beclin-1蛋白相对表达水平。结果与正常对照组相比,空白对照组、NC组A549/DDP细胞eIF5A-2 mRNA相对表达水平显著升高(均P<0.05);与空白对照组、NC组相比,eIF5A-2-SiRNA组细胞凋亡率显著升高,细胞IC50、自噬小体数目、eIF5A-2、LC3Ⅱ及Beclin-1蛋白相对表达水平显著降低(均P<0.05)。结论eIF5A-2下调可降低人肺癌细胞株A549/DDP耐药性,可能与下调LC3Ⅱ、Beclin-1表达,抑制自噬作用有关。 展开更多
关键词 真核翻译起始因子5A-2 肺癌 耐药 自噬
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Roles of HDAC2, eIF5, and eIF6 in Lung Cancer Tumorigenesis 被引量:1
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作者 Shao-xin CAI Wen-shu CHEN +3 位作者 Wei ZENG Xue-fei CHENG Meng-bo LIN Jin-si WANG 《Current Medical Science》 2021年第4期764-769,共6页
Objective The expression levels of histone deacetylase 2(HDAC2),eukaryotic initiation factor 5(eIF5),and eukaryotic initiation factor 6(eIF6),and relationship between HDAC2 and eIF5 or eIF6 in lung cancer tissues were... Objective The expression levels of histone deacetylase 2(HDAC2),eukaryotic initiation factor 5(eIF5),and eukaryotic initiation factor 6(eIF6),and relationship between HDAC2 and eIF5 or eIF6 in lung cancer tissues were investigated,in order to charify the relationship between HDAC2 and the prognosis of lung cancer patients and its influence on the expression of eIF5 and eIF6.Methods The expression of HDAC2,eIF5,and eIF6 in lung cancer tissues was detected by quantitative reverse transcription polymerase chain reaction.The expression correlation between HDAC2 and eIF5 or eIF6 was tested using a t test.The correlation between HDAC2 and eIF5 or eIF6 was analyzed using the TCGA database.The identified cells were constructed with small interfering siRNA and HDAC2 overexpression plasmid.The proliferation and migration ability of the identified cells was investigated by CCK8 and Transwell assays,respectively.Results HDAC2,eIF5,and eIF6 were overexpressed in lung cancer tissues,and HDAC2 expression level was negatively correlated with the prognosis of lung cancer patients.HDAC2 expression level was positively correlated with eIF5 and eIF6 expression levels.HDAC2 could regulate the expression of eIF5 and eIF6.The regulation of proliferation and invasion of lung cancer cells by HDAC2 depended on eIF5 and eIF6.Conclusion HDAC2,eIF5,and eIF6 were closely related with lung cancer tumorigenesis,which might be potential biological markers and therapeutic targets for lung cancer. 展开更多
关键词 histone deacetylase 2 eukaryotic initiation factor 5 eukaryotic initiation factor 6 lung cancer
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Valproate reduces retinal ganglion cell apoptosis in rats after optic nerve crush 被引量:2
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作者 Feng Pan Dan Hu +3 位作者 Li-Juan Sun Qian Bai Yu-Sheng Wang Xu Hou 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第7期1607-1612,共6页
The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neuro... The retinal ganglion cells of the optic nerve have a limited capacity for self-repair after injury.Valproate is a histone deacetylase inhibitor and multitarget drug,which has been demonstrated to protect retinal neurons.In this study,we established rat models of optic nerve-crush injury and injected valproate into the vitreous cavity immediately after modeling.We evaluated changes in the ultrastructure morphology of the endoplasmic reticulum of retinal ganglion cells over time via transmission electron microscope.Immunohistochemistry and western blot assay revealed that valproate upregulated the expression of the endoplasmic reticulum stress marker glucose-regulated protein 78 and downregulated the expression of transcription factor C/EBP homologous protein,phosphorylated eukaryotic translation initiation factor 2α,and caspase-12 in the endoplasmic reticulum of retinal ganglion cells.These findings suggest that valproate reduces apoptosis of retinal ganglion cells in the rat after optic nerve-crush injury by attenuating phosphorylated eukaryotic translation initiation factor 2α-C/EBP homologous protein signaling and caspase-12 activation during endoplasmic reticulum stress.These findings represent a newly discovered mechanism that regulates how valproate protects neurons. 展开更多
关键词 APOPTOSIS C/EBP homologous protein CASPASE-12 endoplasmic reticulum glucose-regulated protein 78 optic nerve crush phosphorylated eukaryotic translation initiation factor 2α retinal ganglion cells unfolded protein response valproate
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EIF3h在结直肠癌组织中的表达及临床病理意义 被引量:9
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作者 吴继华 张建中 +5 位作者 崔彦 冯凯 周金莲 景青萍 尚乐 丁华野 《第三军医大学学报》 CAS CSCD 北大核心 2013年第23期2582-2585,共4页
目的探讨真核翻译起始因子3h(eukaryotic translation initiation factor 3 subunit h,EIF3h)在结直肠癌组织中的表达及其临床病理学意义,并分析在结直肠癌组织中EIF3h和Ki-67表达的关系。方法应用免疫组化EnVision法检测76例结直肠癌... 目的探讨真核翻译起始因子3h(eukaryotic translation initiation factor 3 subunit h,EIF3h)在结直肠癌组织中的表达及其临床病理学意义,并分析在结直肠癌组织中EIF3h和Ki-67表达的关系。方法应用免疫组化EnVision法检测76例结直肠癌组织、35例结直肠腺瘤组织、20例距癌10 cm的肠黏膜组织中EIF3h的表达水平。结果 EIF3h在结直肠癌组织、腺瘤组织、距癌10 cm的肠黏膜组织中表达的阳性率分别为86.84%(66/76)、31.43%(11/35)、10.00%(2/20),3组间差异有统计学意义(P<0.01)。EIF3h的表达与肿瘤浸润深度、有无淋巴结转移相关(P<0.01);与患者的性别、年龄、肿瘤大小和分化程度无关(P>0.05)。结直肠癌组织中EIF3h与Ki-67的表达呈正相关(r=0.42,P<0.01)。结论 EIF3h在结直肠癌组织中呈高表达,提示其可能与结直肠癌的发生、发展密切相关。联合检测EIF3h和Ki-67在结直肠癌中的表达,有助于结直肠癌的诊断和预后的评估。 展开更多
关键词 结直肠肿瘤 EIF3h 免疫组化
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