转录因子调控自噬的研究进展

The Regulatory Mechanisms of Transcription Factors in Autophagy

自噬是一种在进化中高度保守的程序性降解过程,对于维持机体健康至关重要。作为一种基本的细胞代谢过程,自噬参与调控细胞应激适应、干细胞分化、免疫调节、学习记忆等生物学功能,其异常可直接导致免疫功能紊乱、神经退行性疾病和肿瘤等疾病的发生。揭示细胞自噬调控机制有助于为自噬相关疾病提供有效的药物靶点及新的干预措施。研究显示,当细胞面临不同应激条件时,FOXO、p53、TFEB等转录因子严格调节细胞自噬的进程,并参与相关疾病发生的调控。本综述将重点总结转录因子FOXO、p53和TFEB调控细胞自噬发生的分子机制,并阐明其对于肿瘤等疾病发生的调控作用,以期为探究并揭示其他转录因子在细胞自噬中的调控作用提供科学依据。

Autophagy is a highly evolutionarily conserved programmed degradation process that is essential for maintaining organism health.As a fundamental cellular metabolic process,autophagy is involved in regulating biological activities such as cell stress adaptation,stem cell differentiation,immunoregulation,learning and memory.However,the dysfunction of autophagy directly leads to various diseases including immune inflammatory disorders,neurodegenerative diseases and tumorigenesis.Uncovering the regulatory mechanism of autophagy help provide effective drug targets and therapeutic interventions for autophagyrelated diseases.Previous studies have shown that many transcription factors such as FOXO,p53,and TFEB strictly and specifically regulate the process of autophagy when cells are exposed to different extracellular stress,thus enhancing or suppressing related diseases progression.This review presents an overview of the molecular mechanisms of FOXO,p53 and TFEB in regulating autophagy and elucidates their regulatory roles in diseases including tumors,in order to provide scientific and reeasonable clues for further unravelling novel functions of other transcription factors in autophagy.