E3 ubiquitin ligases are a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome.Therefore,E3 ubiquitin ligases play an essential role in a...E3 ubiquitin ligases are a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome.Therefore,E3 ubiquitin ligases play an essential role in a variety of biological processes including cell cycle regulation,proliferation and apoptosis.E3 ubiquitin ligases are often found overexpressed in human cancers,including lung cancer,and their deregulation has been shown to contribute to cancer development.However,the lack of specific inhibitors in clinical trials is a major issue in targeting E3 ubiquitin ligases with currently only one E3 ubiquitin ligase inhibitor being tested in the clinical setting.In this review,we focus on E3 ubiquitin ligases that have been found deregulated in lung cancer.Furthermore,we discuss the processes in which they are involved and evaluate them as potential anti-cancer targets.By better understanding the mechanisms by which E3 ubiquitin ligases regulate biological processes and their exact role in carcinogenesis,we can improve the development of specific E3 ubiquitin ligase inhibitors and pave the way for novel treatment strategies for cancer patients.展开更多
目的探讨食管鳞状细胞癌中DNA结合抑制蛋白-3(inhibitors of DNA binding 3,ID-3)的表达及临床意义。方法应用免疫组化SP法对109例食管鳞癌组织、40例切缘正常组织进行ID-3免疫组化染色,检测癌组织、正常食管黏膜组织中ID-3的表达,并分...目的探讨食管鳞状细胞癌中DNA结合抑制蛋白-3(inhibitors of DNA binding 3,ID-3)的表达及临床意义。方法应用免疫组化SP法对109例食管鳞癌组织、40例切缘正常组织进行ID-3免疫组化染色,检测癌组织、正常食管黏膜组织中ID-3的表达,并分析ID-3的表达与食管鳞癌临床病理特征的关系。结果食管鳞癌组织中ID-3蛋白的表达显著高于切缘正常组织(P<0.01),ID-3蛋白表达与肿瘤分化呈正相关(P<0.01),ID-3蛋白表达与患者的年龄、性别、浸润深度及是否伴淋巴结转移均无关。结论 ID-3高表达可能是食管鳞癌的一个重要的分子学改变,可能在食管鳞癌的发生、发展中起重要作用。展开更多
目的构建转录因子E2-2基因腺病毒载体,观测内皮祖细胞(endothelial progenitor cells,EPCs)过表达E2-2基因对DNA结合抑制因子-1(inhibitor of DNA binding/differentiation,ID1)表达的影响。方法分离、培养并鉴定小鼠骨髓EPCs。RT-PCR...目的构建转录因子E2-2基因腺病毒载体,观测内皮祖细胞(endothelial progenitor cells,EPCs)过表达E2-2基因对DNA结合抑制因子-1(inhibitor of DNA binding/differentiation,ID1)表达的影响。方法分离、培养并鉴定小鼠骨髓EPCs。RT-PCR法扩增E2-2基因CDs全长DNA,克隆入载体pTG19-T后,亚克隆入腺病毒穿梭载体pAdTrack-CMV中,构建pAdTrack/E2-2重组载体,与pAdEasy-1骨架质粒同源重组形成重组病毒pAd/E2-2,经293细胞包装,获具高效感染力的重组pAd/E2-2病毒。将该病毒感染EPCs,倒置显微镜观测经感染的EPCs的GFP表达情况。CCK-8(cell count kit-8)法检测病毒pAd/E2-2对EPCs生长、增殖的影响。RT-PCR、Western blot分别检测经感染的EPCs中E2-2与ID1基因及其编码蛋白的表达情况,并予以定量分析。结果分离、培养并鉴定到小鼠骨髓EPCs。克隆到2013 bp的E2-2基因,并获得高效感染力的重组pAd/E2-2病毒。CCK-8法检测表明,与对照比较,过表达E2-2的EPCs的生长、增殖速度减慢,48h开始变得尤为明显(P<0.01);RT-PCR、Western blot及定量分析结果显示,E2-2能下调ID1的表达,与对照比较,差异具统计学意义(P<0.01)。结论分离、培养并鉴定小鼠骨髓EPCs,克隆出E2-2基因,证实E2-2能明显抑制EPCs的生长、增殖,并能下调ID1基因的表达。展开更多
信号转导与转录激活因子3 (Signal transducer and activator of transcription 3, STAT3)是一种在细胞中参与大量细胞因子及生长因子应答的信号转导蛋白,负责调控细胞的生长、增殖、分化以及凋亡等一系列重要的生理过程。研究发现,STAT...信号转导与转录激活因子3 (Signal transducer and activator of transcription 3, STAT3)是一种在细胞中参与大量细胞因子及生长因子应答的信号转导蛋白,负责调控细胞的生长、增殖、分化以及凋亡等一系列重要的生理过程。研究发现,STAT3的持续性活化与肿瘤的发生发展密切相关。抑制STAT3信号通路的异常活化已成为抗肿瘤药物研发的热门靶点之一。本文从作用于STAT3蛋白的N末端结构域、DNA结合域、SH2结构域以及C末端转录活化结构域的角度,总结了近年来STAT3抗肿瘤抑制剂的研究进展。展开更多
文摘E3 ubiquitin ligases are a large family of proteins that catalyze the ubiquitination of many protein substrates for targeted degradation by the 26S proteasome.Therefore,E3 ubiquitin ligases play an essential role in a variety of biological processes including cell cycle regulation,proliferation and apoptosis.E3 ubiquitin ligases are often found overexpressed in human cancers,including lung cancer,and their deregulation has been shown to contribute to cancer development.However,the lack of specific inhibitors in clinical trials is a major issue in targeting E3 ubiquitin ligases with currently only one E3 ubiquitin ligase inhibitor being tested in the clinical setting.In this review,we focus on E3 ubiquitin ligases that have been found deregulated in lung cancer.Furthermore,we discuss the processes in which they are involved and evaluate them as potential anti-cancer targets.By better understanding the mechanisms by which E3 ubiquitin ligases regulate biological processes and their exact role in carcinogenesis,we can improve the development of specific E3 ubiquitin ligase inhibitors and pave the way for novel treatment strategies for cancer patients.
文摘目的探讨食管鳞状细胞癌中DNA结合抑制蛋白-3(inhibitors of DNA binding 3,ID-3)的表达及临床意义。方法应用免疫组化SP法对109例食管鳞癌组织、40例切缘正常组织进行ID-3免疫组化染色,检测癌组织、正常食管黏膜组织中ID-3的表达,并分析ID-3的表达与食管鳞癌临床病理特征的关系。结果食管鳞癌组织中ID-3蛋白的表达显著高于切缘正常组织(P<0.01),ID-3蛋白表达与肿瘤分化呈正相关(P<0.01),ID-3蛋白表达与患者的年龄、性别、浸润深度及是否伴淋巴结转移均无关。结论 ID-3高表达可能是食管鳞癌的一个重要的分子学改变,可能在食管鳞癌的发生、发展中起重要作用。
文摘信号转导与转录激活因子3 (Signal transducer and activator of transcription 3, STAT3)是一种在细胞中参与大量细胞因子及生长因子应答的信号转导蛋白,负责调控细胞的生长、增殖、分化以及凋亡等一系列重要的生理过程。研究发现,STAT3的持续性活化与肿瘤的发生发展密切相关。抑制STAT3信号通路的异常活化已成为抗肿瘤药物研发的热门靶点之一。本文从作用于STAT3蛋白的N末端结构域、DNA结合域、SH2结构域以及C末端转录活化结构域的角度,总结了近年来STAT3抗肿瘤抑制剂的研究进展。
