转移消失蛋白(missing in metastasis,MIM)是一种重要的胞内膜调控蛋白,属于inverse BAR(I-BAR)家族成员,能结合细胞膜并在细胞极化、运动和内吞作用等过程中发挥调节功能,其表达异常与多种疾病尤其是肿瘤发生或转移相关,在神经系统、...转移消失蛋白(missing in metastasis,MIM)是一种重要的胞内膜调控蛋白,属于inverse BAR(I-BAR)家族成员,能结合细胞膜并在细胞极化、运动和内吞作用等过程中发挥调节功能,其表达异常与多种疾病尤其是肿瘤发生或转移相关,在神经系统、循环系统和生殖泌尿系统中也有一定作用.MIM蛋白的生物学功能包括调节肌动蛋白细胞骨架、与皮动蛋白等其他蛋白相互作用、参与细胞信号通路调控、改变细胞膜形态并促进细胞极化等,在结构上表现出典型I-BAR家族成员特征,借助其N端的I-BAR区域自聚合形成二聚体,促使细胞膜形成伪足状突起,甚至可以调控人造磷脂囊泡,但二聚体的形成也可被靶向的多肽等抑制剂阻断.除作用于蛋白I-BAR,RPTP结合域的特异性多肽外,MIM也可被RNAi干涉,在肿瘤生物治疗领域具有开发潜力.本文回顾了MIM蛋白相关医学研究进展,综述了MIM蛋白已知的生物功能,分析了MIM蛋白靶向治疗及其他应用前景,并提出了可能的研究新方向、新思路.展开更多
Patients treated with the cisplatin often develop strong resistance to the drug after prolonged treatments, ultimately resulting in limited clinical efficacy. One of the possible mechanisms is that the internalized co...Patients treated with the cisplatin often develop strong resistance to the drug after prolonged treatments, ultimately resulting in limited clinical efficacy. One of the possible mechanisms is that the internalized compound may be inactivated before getting access to the nucleus where cisplatin forms a complex with the genomic DNA and triggers a cell death program. However, the nature and intracellular fate of inactivated cisplatin is poorly illustrated. In the present study, we reported for the first time the presence of platinum nanoparticles(Pt-NPs) in the cytoplasm of cells treated with cisplatin. Further analysis also evidenced a correlation of the increased intracellular PtNPs formation with cisplatin resistance, and confirmed the process was glutathione S-transferase relevant. Our data suggest that tumor cells may develop cisplatin resistance by converting the drug into less toxic intracellular Pt-NPs, thereby impeding the drug from targeting its substrates.展开更多
文摘转移消失蛋白(missing in metastasis,MIM)是一种重要的胞内膜调控蛋白,属于inverse BAR(I-BAR)家族成员,能结合细胞膜并在细胞极化、运动和内吞作用等过程中发挥调节功能,其表达异常与多种疾病尤其是肿瘤发生或转移相关,在神经系统、循环系统和生殖泌尿系统中也有一定作用.MIM蛋白的生物学功能包括调节肌动蛋白细胞骨架、与皮动蛋白等其他蛋白相互作用、参与细胞信号通路调控、改变细胞膜形态并促进细胞极化等,在结构上表现出典型I-BAR家族成员特征,借助其N端的I-BAR区域自聚合形成二聚体,促使细胞膜形成伪足状突起,甚至可以调控人造磷脂囊泡,但二聚体的形成也可被靶向的多肽等抑制剂阻断.除作用于蛋白I-BAR,RPTP结合域的特异性多肽外,MIM也可被RNAi干涉,在肿瘤生物治疗领域具有开发潜力.本文回顾了MIM蛋白相关医学研究进展,综述了MIM蛋白已知的生物功能,分析了MIM蛋白靶向治疗及其他应用前景,并提出了可能的研究新方向、新思路.
基金Funded by the National Key Basic Research Program of China (2011CB933503)the National Natural Science Foundation of China (NSFC) for Key Project of International Cooperation (61420106012)+2 种基金the Special Funds of National Natural Science Foundation of China For Basic Research Projects of Scientific Instruments (61127002)the Special Project on the Development of National Key Scientific Instruments and Equipment of China (2011YQ03013403)China Postdoctoral Science Foundation funded project (2013M541592)
文摘Patients treated with the cisplatin often develop strong resistance to the drug after prolonged treatments, ultimately resulting in limited clinical efficacy. One of the possible mechanisms is that the internalized compound may be inactivated before getting access to the nucleus where cisplatin forms a complex with the genomic DNA and triggers a cell death program. However, the nature and intracellular fate of inactivated cisplatin is poorly illustrated. In the present study, we reported for the first time the presence of platinum nanoparticles(Pt-NPs) in the cytoplasm of cells treated with cisplatin. Further analysis also evidenced a correlation of the increased intracellular PtNPs formation with cisplatin resistance, and confirmed the process was glutathione S-transferase relevant. Our data suggest that tumor cells may develop cisplatin resistance by converting the drug into less toxic intracellular Pt-NPs, thereby impeding the drug from targeting its substrates.
