单位：[1]Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210096, China[2]Jiangsu Provincial KeyLaboratory of Critical Care Medicine, Department of Critical Care Medicine, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China[3]Department ofPathology, School of Medicine, Southeast University, Nanjing 210009, China[4]Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China[5]Shenzhen Research Institute, Southeast University, 19 Gaoxin South 4th Road, Nanshan District, Shenzhen 518063, China[6]Jiangsu Province Hi-Tech Key Laboratory forBiomedical Research, School of Life Science and Technology, Southeast University, Nanjing 210096, China[7]Jiangsu Provincial Key Laboratory of Critical Care Medicine, School ofLife Science and Technology, Southeast University, Nanjing 210096, China
Activation of the pro-apoptotic genes by the p53 family is a critical step in induction of apoptosis. However, the molecular signaling underlying their suppression remains largely unknown. Here, we report a general role of QSER1 in preventing apoptosis. QSER1 is widely up-regulated in multiple cancers, and its up-regulation correlates with poor clinic outcomes. QSER1 knockdown significantly promotes apoptosis in both p53 wild type and mutant cancer cells. Interestingly, we show that QSER1 and p53 occupy distinct cis-regulatory regions in a common subset of the pro-apoptotic genes, and function antagonistically to maintain their proper expression. Furthermore, we identify a key regulatory DNA element named QSER1 binding site in PUMA (QBP). Deletion of QBP de-represses PUMA and induces apoptosis. Mechanistically, QSER1 functions together with SIN3A to suppress PUMA in a p53-dependent and -independent manner, suggesting that QSER1 inhibition might be a potential therapeutic strategy to induce apoptosis in cancers.
基金：
National Key R&D Program of China [2018YFA0800100]; National Natural Science Foundation of China [32030017, 31970617, 31970626]; Shenzhen Science and Technology Program [JCYJ20210324133602008, JCYJ20210324133601005]; Jiangsu Provincial Key Laboratory of Critical Care Medicine [JSKLCCM2021-01-004]; Fundamental Research Funds for the Central Universities; ZhiShan Scholar Program of Southeast University [2242022R40063]
第一作者单位：[1]Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210096, China
共同第一作者：
通讯作者：
通讯机构：[1]Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University, Nanjing 210096, China[5]Shenzhen Research Institute, Southeast University, 19 Gaoxin South 4th Road, Nanshan District, Shenzhen 518063, China[6]Jiangsu Province Hi-Tech Key Laboratory forBiomedical Research, School of Life Science and Technology, Southeast University, Nanjing 210096, China[7]Jiangsu Provincial Key Laboratory of Critical Care Medicine, School ofLife Science and Technology, Southeast University, Nanjing 210096, China
推荐引用方式(GB/T 7714)：
Zhao Xiru,Fang Ke,Liu Xiaoxu,et al.QSER1 preserves the suppressive status of the pro-apoptotic genes to prevent apoptosis[J].CELL DEATH AND DIFFERENTIATION.2022,doi:10.1038/s41418-022-01085-x.
APA：
Zhao, Xiru,Fang, Ke,Liu, Xiaoxu,Yao, Ruihuan,Wang, Min...&Luo, Zhuojuan.(2022).QSER1 preserves the suppressive status of the pro-apoptotic genes to prevent apoptosis.CELL DEATH AND DIFFERENTIATION,,
MLA：
Zhao, Xiru,et al."QSER1 preserves the suppressive status of the pro-apoptotic genes to prevent apoptosis".CELL DEATH AND DIFFERENTIATION .(2022)
生物学