A coherent FOXO3-SNAI2 feed-forward loop in autophagy

作者：Xiaowei Guo, Zhuojie Li, Xiaojie Zhu, Meixiao Zhan, Chenxi Wu, Xiang Ding, Kai Peng, Wenzhe Li, Xianjue Ma, Zhongwei Lv, Ligong Lu, Lei Xue · 发表于：Proceedings of the National Academy of Sciences · 年份：2022 · DOI：10.1073/pnas.2118285119 · 被引用次数：25 · 研究领域：Autophagy in Disease and Therapy、FOXO transcription factor regulation、CRISPR and Genetic Engineering

Significance Understanding autophagy regulation is instrumental in developing therapeutic interventions for autophagy-associated disease. Here, we identified SNAI2 as a regulator of autophagy from a genome-wide screen in HeLa cells. Upon energy stress, SNAI2 is transcriptionally activated by FOXO3 and interacts with FOXO3 to form a feed-forward regulatory loop to reinforce the expression of autophagy genes. Of note, SNAI2-increased FOXO3-DNA binding abrogates CRM1-dependent FOXO3 nuclear export, illuminating a pivotal role of DNA in the nuclear retention of nucleocytoplasmic shuttling proteins. Moreover, a dFoxO-Snail feed-forward loop regulates both autophagy and cell size in Drosophila , suggesting this evolutionarily conserved regulatory loop is engaged in more physiological activities.