溶酶体生成转录调节因子TFEB的调控机制研究进展

Research progress on the regulation mechanism of lysosomal biogenesis transcription regulator TFEB

转录因子EB(transcription factor EB, TFEB)是小眼畸形相关转录因子(microphthalmia/transcription factor E,MiTF)家族成员之一,是控制影响溶酶体功能、自噬和细胞代谢等相关基因表达的转录因子。TFEB的活性主要受哺乳动物雷帕霉素靶蛋白复合物1(mammalian target of rapamycin complex 1,mTORC1)磷酸化修饰的影响并和其亚细胞定位有着密切的关系,但是越来越多的研究表明其他的一些激酶也可以以不依赖于mTORC1的方式对TFEB进行磷酸化修饰,除此之外,一些其他的修饰也会参与调控TFEB的活性,TFEB的活性状态直接影响了细胞的生理状态及肿瘤、神经退行性等疾病的发生。因此,TFEB调控机制的阐明有助于深入了解这些疾病的发病机制,也为防治这些疾病提供了新的靶点。

Lysosomal biogenesis transcription factor EB(TFEB)is a member of the microphthalmia/transcription factor E(MiTF)family to control the expression of related genes involving in lysosomal function,autophagy and cell metabolism.The activity of TFEB is mainly regulated by mTORCl(mammalian target of rapamycin complex 1)mediated phosphorylation and is closely related to its subcellular localization.However,a growing body of research shows that other kinases can also phosphorylate TFEB independent of mTORC1.In addition,some other modifications are also involved in regulating the activity and subcellular localization of TFEB.So the activity of TFEB directly affects the physiological state of cells and the occurrence of diseases such as tumors and neurodegenerative diseases.Therefore,the elucidation of the regulatory mechanism of TFEB helps to understand the pathogenesis of these diseases and provides new targets for the prevention and treatment of these diseases.