Guo, X., Li, Z., Zhu, X., Zhan, M., Wu, C., Ding, X., Peng, K., Li, W., Ma, X., Lv, Z., Lu, L., Xue, L. (2022). A coherent FOXO3-SNAI2 feed-forward loop in autophagy. Proc. Natl. Acad. Sci. U.S.A. 119(11): e2118285119.
FlyBase ID
FBrf0252929
Publication Type
Research paper
Abstract
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.
