目的:探索EIF4A3的表达与高级别浆液性卵巢癌患者临床病理特征和预后的关系,明确其在高级别浆液性卵巢癌发生发展过程中的作用。方法:采用免疫组织化学方法检测EIF4A3在高级别浆液性卵巢癌组织、交界性卵巢肿瘤组织以及正常输卵管组织...目的:探索EIF4A3的表达与高级别浆液性卵巢癌患者临床病理特征和预后的关系,明确其在高级别浆液性卵巢癌发生发展过程中的作用。方法:采用免疫组织化学方法检测EIF4A3在高级别浆液性卵巢癌组织、交界性卵巢肿瘤组织以及正常输卵管组织中的表达情况,分析其表达对高级别浆液性卵巢癌临床病理特征及预后的影响。通过TIMER数据库分析EIF4A3在泛癌中的表达水平。通过Sangerbox工具分析EIF4A3表达在泛癌中的预后情况。通过cBioportal网站分析EIF4A3在卵巢癌组织中基因突变的情况。通过GeneMANIA网站构建与EIF4A3共表达基因网络图,其中与EIF4A3最有关系的5个基因分别为ETF1、CENPX、DDX21、DDX31和JMJD6。结果:EIF4A3在高级别浆液性卵巢癌组织中的表达高于交界性卵巢肿瘤和正常输卵管组织(P P P < 0.05)。结论:EIF4A3在高级别浆液性卵巢癌中高表达,与临床病理特征及不良预后有关,EIF4A3可能参与卵巢癌的发生和发展。展开更多
Eukaryotic initiation factor 4 A(eIF4A)plays critical roles during translation initiation of cellular mRNAs by forming the cap-binding eIF4F complex,recruiting the 40S small ribosome subunit,and scanning the 5’untran...Eukaryotic initiation factor 4 A(eIF4A)plays critical roles during translation initiation of cellular mRNAs by forming the cap-binding eIF4F complex,recruiting the 40S small ribosome subunit,and scanning the 5’untranslated region(5’UTR)for the start codon.eIF4A1 and eIF4A2,two isoforms of eIF4A,are highly conserved and exchange freely within eIF4F complexes.The understanding of their biological and molecular functions remains incomplete if not fragmentary.In this study,we showed that eIF4A1 and eIF4A2 exhibit different expression patterns during B-cell development and activation.Mouse genetic analyses showed that they play critical but differential roles during B-cell development and humoral immune responses.While eIF4A1 controls global protein synthesis,eIF4A2 regulates the biogenesis of 18S ribosomal RNA and the 40S ribosome subunit.This study demonstrates the distinct cellular and molecular functions of eIF4A1 and eIF4A2 and reveals a new role of eIF4A2 in controlling 40S ribosome biogenesis.展开更多
基金supported by grants from The National Natural Science Foundation of China(81672478,81772671)the Beijing Natural Science Foundation(7151002)+1 种基金the Beijing Health System High-level Personnel Building Foundation(2013-3-018)the Beijing Laboratory of Biomedical Materials Foundation~~
文摘神经生长因子(NGF)结合细胞表面受体p75NTR (p75神经营养素受体)和TrkA (酪氨酸蛋白激酶A)后介导了细胞分化、细胞生存、凋亡、增殖和侵袭等多个重要的生理病理过程. TrKA能与细胞内多个蛋白质相互作用,但是由于NGF信号通路的复杂性,现在仍有必要发现与之相互作用的蛋白质以更准确地了解NGF信号通路.本研究中我们通过酵母双杂交的方法筛选到了一个新的与TrKA相互作用的蛋白质——真核生物翻译起始因子4A1 (eIF4A1),然后通过谷胱甘肽巯基转移酶融合蛋白沉降实验(GST-pull-down)和免疫共沉淀实验(Co-IP)证明了TrkA和eIF4A1的相互作用.此外NGF能够增强TrkA和eIF4A1的相互作用.在鉴定相互作用位点实验中,我们发现eIF4A1的氨基端结构域和TrkA的TK结构域参与了相互作用. TrkA和e IF4A1共定位在细胞膜上. NGF能够引起TrkA与泛素蛋白63位的赖氨酸连接,而eIF4A1与TrkA相互作用后能够抑制TrkA与泛素蛋白63位的赖氨酸连接.综上,得出结论 e IF4A1通过与TrkA相互作用抑制其泛素化调控NGF信号通路.
文摘目的:探索EIF4A3的表达与高级别浆液性卵巢癌患者临床病理特征和预后的关系,明确其在高级别浆液性卵巢癌发生发展过程中的作用。方法:采用免疫组织化学方法检测EIF4A3在高级别浆液性卵巢癌组织、交界性卵巢肿瘤组织以及正常输卵管组织中的表达情况,分析其表达对高级别浆液性卵巢癌临床病理特征及预后的影响。通过TIMER数据库分析EIF4A3在泛癌中的表达水平。通过Sangerbox工具分析EIF4A3表达在泛癌中的预后情况。通过cBioportal网站分析EIF4A3在卵巢癌组织中基因突变的情况。通过GeneMANIA网站构建与EIF4A3共表达基因网络图,其中与EIF4A3最有关系的5个基因分别为ETF1、CENPX、DDX21、DDX31和JMJD6。结果:EIF4A3在高级别浆液性卵巢癌组织中的表达高于交界性卵巢肿瘤和正常输卵管组织(P P P < 0.05)。结论:EIF4A3在高级别浆液性卵巢癌中高表达,与临床病理特征及不良预后有关,EIF4A3可能参与卵巢癌的发生和发展。
基金supported by the National Natural Science Foundation of China(81830047 and 81961138008 to C.X.,31770950 and 32070877 to W.-H.L.)Sanofi Institute for Biomedical Research(SIBR)。
文摘Eukaryotic initiation factor 4 A(eIF4A)plays critical roles during translation initiation of cellular mRNAs by forming the cap-binding eIF4F complex,recruiting the 40S small ribosome subunit,and scanning the 5’untranslated region(5’UTR)for the start codon.eIF4A1 and eIF4A2,two isoforms of eIF4A,are highly conserved and exchange freely within eIF4F complexes.The understanding of their biological and molecular functions remains incomplete if not fragmentary.In this study,we showed that eIF4A1 and eIF4A2 exhibit different expression patterns during B-cell development and activation.Mouse genetic analyses showed that they play critical but differential roles during B-cell development and humoral immune responses.While eIF4A1 controls global protein synthesis,eIF4A2 regulates the biogenesis of 18S ribosomal RNA and the 40S ribosome subunit.This study demonstrates the distinct cellular and molecular functions of eIF4A1 and eIF4A2 and reveals a new role of eIF4A2 in controlling 40S ribosome biogenesis.
