Open AccessA coherent FOXO3-SNAI2 feed-forward loop in autophagy
Author(s) -
Xiaowei Guo,
Zhuojie Li,
Xiaojie Zhu,
Meixiao Zhan,
Chenxi Wu,
Dongxi Xiang,
Kai Peng,
Wenzhe Li,
Xianjue Ma,
Zhongwei Lv,
Ligong Lu,
Lei Xue
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2118285119
Subject(s) - autophagy , foxo3 , microbiology and biotechnology , biology , regulator , genetics , gene , signal transduction , apoptosis , protein kinase b
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 inDrosophila , suggesting this evolutionarily conserved regulatory loop is engaged in more physiological activities.