机构：[1]Institute of Intervention Vessel, Shanghai 10th People’s Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, 200092 Shanghai, China[2]Hunan Normal University School of Medicine, 410081 Hunan, China[3]Zhuhai Precision Medical Center, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People’s Hospital, Zhuhai Hospital Affiliated with Jinan University, 510630 Guangdong, China[4]College of Traditional Chinese Medicine, North China University of Science and Technology, 063009 Hebei, China[5]Westlake Laboratory of Life Sciences and Biomedicine, 310024 Hangzhou, China[6]National Clinical Research Center for Interventional Medicine, Shanghai 10th People's Hospital, 200072 Shanghai, China
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.
基金：
This work
is supported by National Natural Science Foundation of China Grant
31970536 (to L.X.), Grant 32000547 (to X.G.), and Grant 81771957 (to L.L.);
Shanghai Committee of Science and Technology grants 09DZ2260100 and
19MC1910300 (to L.X.); China Postdoctoral Science Foundation Grant
2000229071 (to X.G.); and Shanghai Shenkang Three Years Action Project
SHDC2020CR2054B (to Z. Lv).
语种：
外文
PubmedID：
中科院(CAS)分区：
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第一作者：
第一作者机构：[1]Institute of Intervention Vessel, Shanghai 10th People’s Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, 200092 Shanghai, China[2]Hunan Normal University School of Medicine, 410081 Hunan, China
共同第一作者：
通讯作者：
通讯机构：[1]Institute of Intervention Vessel, Shanghai 10th People’s Hospital, Shanghai Key Laboratory of Signaling and Diseases Research, School of Life Science and Technology, Tongji University, 200092 Shanghai, China[2]Hunan Normal University School of Medicine, 410081 Hunan, China[3]Zhuhai Precision Medical Center, Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai People’s Hospital, Zhuhai Hospital Affiliated with Jinan University, 510630 Guangdong, China[6]National Clinical Research Center for Interventional Medicine, Shanghai 10th People's Hospital, 200072 Shanghai, China
推荐引用方式(GB/T 7714)：
Guo Xiaowei,Li Zhuojie,Zhu Xiaojie,et al.A coherent FOXO3-SNAI2 feed-forward loop in autophagy.[J].Proceedings of the National Academy of Sciences of the United States of America.2022,119(11):e2118285119.doi:10.1073/pnas.2118285119.
APA：
Guo Xiaowei,Li Zhuojie,Zhu Xiaojie,Zhan Meixiao,Wu Chenxi...&Xue Lei.(2022).A coherent FOXO3-SNAI2 feed-forward loop in autophagy..Proceedings of the National Academy of Sciences of the United States of America,119,(11)
MLA：
Guo Xiaowei,et al."A coherent FOXO3-SNAI2 feed-forward loop in autophagy.".Proceedings of the National Academy of Sciences of the United States of America 119..11(2022):e2118285119
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