A coherent FOXO3-SNAI2 feed-forward loop in autophagy.
Xiaowei GuoZhuojie LiXiaojie ZhuMeixiao ZhanChenxi WuXiang DingKai PengWenzhe LiXianjue MaZhongwei LvLigong LuLei XuePublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
SignificanceUnderstanding 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.
Keyphrases
- transcription factor
- signaling pathway
- dna binding
- cell death
- endoplasmic reticulum stress
- induced apoptosis
- oxidative stress
- pi k akt
- cell cycle arrest
- genome wide
- genome wide identification
- epithelial mesenchymal transition
- dna methylation
- poor prognosis
- physical activity
- high throughput
- single cell
- binding protein
- cell free
- bone marrow