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DEAD-box RNA解旋酶5和转录因子12与肌萎缩侧索硬化症的关系 被引量:2
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作者 林宝勇 徐进超 +5 位作者 应涵韬 蒋欣 刘焕彩 王箐 王巧真 陈燕春 《解剖学报》 CAS CSCD 北大核心 2021年第5期698-705,共8页
目的通过检测DEAD-box RNA解旋酶5(DDX5)和转录因子12(TCF12)在SOD1-G93A突变型肌萎缩侧索硬化症(ALS)转基因小鼠海马中表达情况及其相互作用关系,揭示DDX5和TCF12表达改变与ALS海马病变的关系。方法将42对SOD1-G93A突变型ALS转基因小... 目的通过检测DEAD-box RNA解旋酶5(DDX5)和转录因子12(TCF12)在SOD1-G93A突变型肌萎缩侧索硬化症(ALS)转基因小鼠海马中表达情况及其相互作用关系,揭示DDX5和TCF12表达改变与ALS海马病变的关系。方法将42对SOD1-G93A突变型ALS转基因小鼠和野生型小鼠,按照95 d龄(发病早期)、108 d龄(发病中期)和122 d龄(发病晚期)分为3组,通过RT-PCR、Western blotting和免疫荧光双标记技术,检测DDX5和TCF12在海马中的表达情况,通过免疫共沉淀技术检测DDX5和TCF12蛋白之间是否具有相互作用。结果与同龄野生型小鼠相比,在SOD1-G93A突变型ALS转基因小鼠海马中DDX5和TCF12 m RNA无明显变化,而蛋白在95 d、108 d和122 d表达均上调,差异均有统计学意义。海马齿状回和海马本部均可见DDX5和TCF12阳性细胞,且DDX5和TCF12在海马神经元中表达。SOD1-G93A突变型ALS转基因小鼠海马中DDX5和TCF12免疫阳性反应均较同龄野生型小鼠增强。免疫共沉淀实验检测发现,DDX5和TCF12蛋白质之间存在相互作用。结论DDX5和TCF12蛋白在SOD1-G93A突变型ALS转基因小鼠海马组织中表达上调,DDX5和TCF12表达异常与ALS海马组织病变有关。 展开更多
关键词 肌萎缩侧索硬化症 dead-box解旋酶5 转录因子12 海马 免疫共沉淀技术 SOD1-G93A转基因小鼠
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DEAD-box RNA helicases with special reference to p68:Unwinding their biology,versatility,and therapeutic opportunity in cancer 被引量:1
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作者 Shaheda Tabassum Mrinal K.Ghosh 《Genes & Diseases》 SCIE CSCD 2023年第4期1220-1241,共22页
In the era of advancement,the entire world continues to remain baffled by the increased rate of progression of cancer.There has been an unending search for novel thera-peutic targets and prognostic markers to curb the... In the era of advancement,the entire world continues to remain baffled by the increased rate of progression of cancer.There has been an unending search for novel thera-peutic targets and prognostic markers to curb the oncogenic scenario.The DEAD-box RNA he-licases are a large family of proteins characterized by their evolutionary conserved D-E-A-D(Asp-Glu-Ala-Asp)domain and merit consideration in the oncogenic platform.They perform multidimensional functions in RNA metabolism and also in the pathology of cancers.Their bio-logical role ranges from ribosome biogenesis,RNA unwinding,splicing,modification of second-ary and tertiary RNA structures to acting as transcriptional coactivators/repressors of various important oncogenic genes.They also play a crucial role in accelerating oncogenesis by pro-moting cell proliferation and metastasis.DDX5(p68)is one of the archetypal members of this family of proteins and has gained a lot of attention due to its oncogenic attribute.It is found to be overexpressed in major cancer types such as colon,brain,breast,and prostate cancer.It exhibits its multifaceted nature by not only coactivating genes implicated in cancers but also mediating crosstalk across major signaling pathways in cancer.Therefore,in this review,we aim to illustrate a comprehensive overview of DEAD-box RNA helicases especially p68 by focusing on their multifaceted roles in different cancers and the various signaling pathways affected by them.Further,we have also briefly discoursed the therapeutic interventional approaches with the DEAD-box RNA helicases as the pharmacological targets for designing in-hibitors to pave way for cancer therapy. 展开更多
关键词 CANCER DDX5 dead-box RNA helicases Gene expression ONCOGENE Signaling Therapy Transcription factor
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小鼠DDX5分子结构特征及功能初步探究 被引量:5
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作者 成温玉 何小兵 +1 位作者 贾怀杰 景志忠 《基因组学与应用生物学》 CAS CSCD 北大核心 2021年第5期1983-1992,共10页
为探讨小鼠DDX5的结构特征及生物学功能,本研究采用RT-PCR技术从小鼠脾淋巴细胞中克隆DDX5基因,通过生物信息学软件分析DDX5的遗传演化关系和结构特征,并运用荧光定量PCR检测小鼠DDX5基因的组织表达谱;进一步将DDX5基因亚克隆至真核表... 为探讨小鼠DDX5的结构特征及生物学功能,本研究采用RT-PCR技术从小鼠脾淋巴细胞中克隆DDX5基因,通过生物信息学软件分析DDX5的遗传演化关系和结构特征,并运用荧光定量PCR检测小鼠DDX5基因的组织表达谱;进一步将DDX5基因亚克隆至真核表达载体pCMV-Tag2B,通过Western-blot验证表达后,采用双荧光素酶报告系统检测过表达DDX5对NF-κB和IFN-β启动子激活活性的影响。研究结果显示,小鼠DDX5基因开放阅读框全长1848 bp,编码615个氨基酸,与其它动物的DDX5氨基酸序列同源性非常高(87.7%~98.8%);在小鼠DExD/H解旋酶家族中,DDX5与DDX17遗传距离最近,且与DDX41和DDX3位于同一大支;结构分析显示,DDX5具备典型的DExD核心域和解旋酶C端结构域,但不具备Caspase募集结构域和RIG-I样C端结构;DDX5基因在小鼠心脏表达最高,在外周血淋巴细胞和小肠中表达最低;构建的DDX5真核表达载体能转染HEK293T细胞并成功表达,可显著增强激活NF-κB起始的相对荧光素酶活性,但对IFN-β启动子起始的相对荧光素酶活性无影响。上述结果表明,DDX5可能具有免疫调节的功能,并且参与了NF-κB介导的信号通路,进而为探究鼠源DDX5在病毒感染和免疫学中的作用奠定基础。 展开更多
关键词 DDX5 小鼠 结构特征 基因表达 免疫调节
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