抗增殖蛋白在肿瘤发生发展过程中扮演多种角色

Multifaceted Roles of Prohibitins in the Process of Tumor Occurrence and Development

抗增殖蛋白(prohibitins,PHBs)是一类进化保守的重要蛋白质。哺乳动物细胞中,抗增殖蛋白家族含有2个同源亚型PHB1和PHB2。PHBs涉及多种细胞功能,包括细胞增殖、细胞迁移和细胞凋亡。PHBs的亚细胞定位不同决定其行使不同的功能。细胞膜上的PHBs能够调节膜运输,并与细胞增殖迁移相关。细胞核内的PHBs参与调控转录和细胞周期。线粒体内膜上的PHBs参与维持线粒体基因组和线粒体形态的稳定,并参与线粒体内的凋亡途径。另外,PHBs可以在细胞核和线粒体之间“穿梭”,是细胞核与线粒体交流的重要媒介。近年来,PHBs的研究不断深入,发现PHBs与多种肿瘤的发生和发展密切相关。本文以PHBs在肿瘤发生发展过程中扮演的角色为切入点,从蛋白质的结构和定位,在肿瘤的发生、发展、迁移和凋亡中的作用及其靶向药物几方面进行综述。进一步揭示PHBs在不同类型肿瘤发生发展进程中的分子机制,为开发新的高效的药物靶点奠定了理论基础。

Prohibitins(PHBs)are important proteins that evolve conservatively.The Prohibitin domain family contains two homologous subtypes of PHB1 and PHB2 in mammalian cells.PHBs involve a variety of cellular functions,including cell proliferation,cell migration and cell apoptosis.The subcellular localization of PHBs determines that they perform different functions.The PHBs distributed on membranes can regulate membrane transport,cell proliferation and migration,the PHBs in the nucleus can regulate gene transcription and cell cycle,the PHBs located in the mitochondrial inner membrane can maintain the mitochondrial genome and mitochondrial morphology,and are involved in mitochondrial pathways of apoptosis.Moreover,as an important medium,PHB proteins can"shuttle"between the nucleus and mitochondria.In recent years,with the deepening of the research on PHBs,we can find that PHBs are closely related to occurrence and development of multiple types of tumors.This paper gives a general review from structure and localization of proteins,as well as their functions focusing on the roles of PHBs in occurrence,development,migration and apoptosis of tumors.It lays a theoretical foundation for further revealing the molecular mechanism of PHBs and in the development of different types of tumors to work on more efficient drug targets.