南方科技大学知识苑(SUSTech KC): TFEB, a master regulator of autophagy and biogenesis, unexpectedly promotes apoptosis in response to the cyclopentenone prostaglandin 15d-PGJ2

题名	TFEB, a master regulator of autophagy and biogenesis, unexpectedly promotes apoptosis in response to the cyclopentenone prostaglandin 15d-PGJ2
作者	Yang, Chuan-bin 1,2,3; Liu, Jia 3; Tong, Benjamin Chun-Kit 3; Wang, Zi-ying 3,4; Zhu, Zhou 3; Su, Cheng-fu 3; Sreenivasmurthy, Sravan Gopalkrishnashetty 3; Wu, Jia-xi 3; Iyaswamy, Ashok 3; Krishnamoorthi, Senthilkumar 3; Huang, Shi-ying 1,2; Cheung, King-ho 3; Song, Ju-xian 3,5; Tan, Jie-qiong 6,7; Lu, Jia-hong 8; Li, Min 3
通讯作者	Li, Min
发表日期	2021-08-01
DOI	10.1038/s41401-021-00711-7
发表期刊	ACTA PHARMACOLOGICA SINICA 影响因子和分区
ISSN	1671-4083
EISSN	1745-7254
摘要	Transcriptional factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis, is generally regarded as a pro-survival factor. Here, we identify that besides its effect on autophagy induction, TFEB exerts a pro-apoptotic effect in response to the cyclopentenone prostaglandin 15-deoxy- increment -(12,14)-prostaglandin J2 (15d-PGJ2). Specifically, 15d-PGJ2 promotes TFEB translocation from the cytoplasm into the nucleus to induce autophagy and lysosome biogenesis via reactive oxygen species (ROS) production rather than mTORC1 inactivation. Surprisingly, TFEB promotes rather than inhibits apoptosis in response to 15d-PGJ2. Mechanistically, ROS-mediated TFEB translocation into the nucleus transcriptionally upregulates the expression of ATF4, which is required for apoptosis elicited by 15d-PGJ2. Additionally, inhibition of TFEB activation by ROS scavenger N-acetyl cysteine or inhibition of protein synthesis by cycloheximide effectively compromises ATF4 upregulation and apoptosis in response to 15d-PGJ2. Collectively, these results indicate that ROS-induced TFEB activation exerts a novel role in promoting apoptosis besides its role in regulating autophagy in response to 15d-PGJ2. This work not only evidences how TFEB is activated by 15d-PGJ2, but also unveils a previously unexplored role of ROS-dependent activation of TFEB in modulating cell apoptosis in response to 15d-PGJ2.
关键词	transcriptional factor EB (TFEB) 15-deoxy-Delta-(12,14)-prostaglandin J2 (15d-PGJ2) autophagy and lysosome biogenesis ATF4 ER stress apoptosis
相关链接	[来源记录]
收录类别	SCI
语种	英语
学校署名	其他
资助项目	Hong Kong General Research Fund["GRF/HKBU12101417","GRF/HKBU12100618"] ; National Natural Science Foundation of China[81703487,81773926] ; Shenzhen Science and Technology Innovation Commission["JCYJ20180302174028790","JCYJ20180507184656626"] ; Hong Kong Health and Medical Research Fund["HMRF17182541","HMRF17182551"] ; Hong Kong Baptist University[HKBU/RC-IRCs/17-18/03]
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
WOS类目	Chemistry, Multidisciplinary ; Pharmacology & Pharmacy
WOS记录号	WOS:000686879800004
出版者	NATURE PUBL GROUP
ESI学科分类	PHARMACOLOGY & TOXICOLOGY
来源库	Web of Science
引用统计	被引频次[WOS]：18
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/253225
专题	南方科技大学第一附属医院
作者单位	1.Jinan Univ, Clin Med Coll 2, Shenzhen Peoples Hosp, Dept Geriatr, Shenzhen 518020, Peoples R China 2.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Peoples R China 3.Hong Kong Baptist Univ, Mr & Mrs Ko Chi Ming Ctr Parkinsons Dis Res, Sch Chinese Med, Hong Kong, Peoples R China 4.Jinan Univ, Interdisciplinary Inst Personalized Med Brain Dis, Guangzhou 510632, Peoples R China 5.Guangzhou Univ Chinese Med, Med Coll Acupuncture Moxibust & Rehabil, Guangzhou 510006, Peoples R China 6.Cent South Univ, Ctr Med Genet, Sch Life Sci, Changsha 410006, Peoples R China 7.Cent South Univ, Hunan Key Lab Anim Model Human Dis, Sch Life Sci, Changsha 410006, Peoples R China 8.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
第一作者单位	南方科技大学第一附属医院
推荐引用方式 GB/T 7714	Yang, Chuan-bin,Liu, Jia,Tong, Benjamin Chun-Kit,et al. TFEB, a master regulator of autophagy and biogenesis, unexpectedly promotes apoptosis in response to the cyclopentenone prostaglandin 15d-PGJ2[J]. ACTA PHARMACOLOGICA SINICA,2021.
APA	Yang, Chuan-bin.,Liu, Jia.,Tong, Benjamin Chun-Kit.,Wang, Zi-ying.,Zhu, Zhou.,...&Li, Min.(2021).TFEB, a master regulator of autophagy and biogenesis, unexpectedly promotes apoptosis in response to the cyclopentenone prostaglandin 15d-PGJ2.ACTA PHARMACOLOGICA SINICA.
MLA	Yang, Chuan-bin,et al."TFEB, a master regulator of autophagy and biogenesis, unexpectedly promotes apoptosis in response to the cyclopentenone prostaglandin 15d-PGJ2".ACTA PHARMACOLOGICA SINICA (2021).