Cells interact with the extracellular matrix and generate traction forces,which play fundamental roles in many cytological activities,such as migration and differentiation.The quanti fication of these traction forces ...Cells interact with the extracellular matrix and generate traction forces,which play fundamental roles in many cytological activities,such as migration and differentiation.The quanti fication of these traction forces is a prerequisite for understanding the interaction and regulation between force and functions,which can be accomplished by traction force microscopy(TFM).In TFM,the forces are determined by tracking the displacement of fiducial markers through optical microscopy.The type of fiducial marker,microscopy modality,and image processing algorithms are key factors determining the final resolution of TFM.This review summarizes efforts in three aspects to enhance the performance of TFM and discusses the challenges of further development,particularly from an optical view.展开更多
E3泛素连接酶作为泛素-蛋白酶体系统的核心组分,通过介导靶蛋白的泛素化修饰在维持细胞内蛋白质稳态中发挥着关键作用。近年来,E3泛素连接酶在肿瘤发生发展中的异常调控机制成为研究热点,但不同结构类型的E3泛素连接酶在肿瘤中的具体功...E3泛素连接酶作为泛素-蛋白酶体系统的核心组分,通过介导靶蛋白的泛素化修饰在维持细胞内蛋白质稳态中发挥着关键作用。近年来,E3泛素连接酶在肿瘤发生发展中的异常调控机制成为研究热点,但不同结构类型的E3泛素连接酶在肿瘤中的具体功能及调控机制仍有待系统解析。因此,系统梳理不同类型的E3泛素连接酶在肿瘤发生发展中的作用机制,对于阐释肿瘤的分子病理机制和开发新型靶向治疗策略具有重要的理论与临床价值。本文首先对E3泛素连接酶的分类及结构特征进行阐述,重点解析HECT(homologous to E6AP carboxyl-terminus)、RING(really interesting new gene)、RBR(RING-between-RING)和U-box家族E3泛素连接酶的结构域组成及转移泛素的作用机制;其次,深入探讨一些典型的E3泛素连接酶在4种常见的高发恶性肿瘤(肺癌、肝癌、结直肠癌和乳腺癌)发生发展过程中呈现的双重作用、调控的靶蛋白及相关信号通路,揭示E3泛素连接酶在肿瘤进展及耐药性调控中的分子机制;最后,总结E3泛素连接酶作为肿瘤治疗靶点的最新研究进展及潜在治疗策略,并探讨靶向E3泛素连接酶治疗策略的疗效和安全性风险等挑战。未来还需进一步整合结构生物学、高通量筛选和人工智能辅助药物设计等多学科交叉手段,推动E3泛素连接酶在肿瘤诊疗领域的深入发展,为改善肿瘤患者预后、提升治疗效果带来新的希望。展开更多
基金supported by the Major Research Instrument Development Project of the National Natural Science Foundation of China(32527801)the National Natural Science Foundation of China(32301168)+1 种基金the Ningbo Natural Science Foundation of China(2023J351)the Yongjiang Innovative Talents Project of Ningbo City(2024A-172-G).
文摘Cells interact with the extracellular matrix and generate traction forces,which play fundamental roles in many cytological activities,such as migration and differentiation.The quanti fication of these traction forces is a prerequisite for understanding the interaction and regulation between force and functions,which can be accomplished by traction force microscopy(TFM).In TFM,the forces are determined by tracking the displacement of fiducial markers through optical microscopy.The type of fiducial marker,microscopy modality,and image processing algorithms are key factors determining the final resolution of TFM.This review summarizes efforts in three aspects to enhance the performance of TFM and discusses the challenges of further development,particularly from an optical view.
文摘E3泛素连接酶作为泛素-蛋白酶体系统的核心组分,通过介导靶蛋白的泛素化修饰在维持细胞内蛋白质稳态中发挥着关键作用。近年来,E3泛素连接酶在肿瘤发生发展中的异常调控机制成为研究热点,但不同结构类型的E3泛素连接酶在肿瘤中的具体功能及调控机制仍有待系统解析。因此,系统梳理不同类型的E3泛素连接酶在肿瘤发生发展中的作用机制,对于阐释肿瘤的分子病理机制和开发新型靶向治疗策略具有重要的理论与临床价值。本文首先对E3泛素连接酶的分类及结构特征进行阐述,重点解析HECT(homologous to E6AP carboxyl-terminus)、RING(really interesting new gene)、RBR(RING-between-RING)和U-box家族E3泛素连接酶的结构域组成及转移泛素的作用机制;其次,深入探讨一些典型的E3泛素连接酶在4种常见的高发恶性肿瘤(肺癌、肝癌、结直肠癌和乳腺癌)发生发展过程中呈现的双重作用、调控的靶蛋白及相关信号通路,揭示E3泛素连接酶在肿瘤进展及耐药性调控中的分子机制;最后,总结E3泛素连接酶作为肿瘤治疗靶点的最新研究进展及潜在治疗策略,并探讨靶向E3泛素连接酶治疗策略的疗效和安全性风险等挑战。未来还需进一步整合结构生物学、高通量筛选和人工智能辅助药物设计等多学科交叉手段,推动E3泛素连接酶在肿瘤诊疗领域的深入发展,为改善肿瘤患者预后、提升治疗效果带来新的希望。
