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.
Hunan Normal University School of Medicine, 410081 Hunan, China.
Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2118285119. doi: 10.1073/pnas.2118285119. Epub 2022 Mar 10.
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 , suggesting this evolutionarily conserved regulatory loop is engaged in more physiological activities.
意义
理解自噬调控对于开发与自噬相关疾病的治疗干预措施至关重要。在这里，我们从 HeLa 细胞的全基因组筛选中鉴定出 SNAI2 是自噬的调节剂。在能量应激下，SNAI2 被 FOXO3 转录激活，并与 FOXO3 相互作用形成正反馈调节环，以增强自噬基因的表达。值得注意的是，SNAI2 增加的 FOXO3-DNA 结合消除了 CRM1 依赖性 FOXO3 核输出，阐明了 DNA 在核保留核质穿梭蛋白中的关键作用。此外，dFoxO-Snail 正反馈环调节 中的自噬和细胞大小，表明这个进化上保守的调节环参与了更多的生理活动。
Zotero 插件
