Rapamycin recruits SIRT2 for FKBP12 deacetylation during mTOR activity modulation in innate immunity

doi:10.1016/j.isci.2021.103177

	Rapamycin recruits SIRT2 for FKBP12 deacetylation during mTOR activity modulation in innate immunity
	Hu, Lin 1; Chen, Fuxian 1; Wu, Chao 1; Wang, Jun 2; Chen, Si-si 3,4; Li, Xiang-rong 1; Wang, Jing 1; Wu, Linpeng 1; Ding, Jian-ping 3,4; Wang, Jian-chuan 5
刊名	ISCIENCE
	2021-11-19
卷号	24 期号:11 页码:22
DOI	10.1016/j.isci.2021.103177
通讯作者	Deng, Wei(dengwei0328@suda.edu.cn) ; Luo, Cheng(cluo@simm.ac.cn) ; Chin, Y. Eugene(chinyue@suda.edu.cn)
英文摘要	The mammalian target of rapamycin (mTOR) is a serine- threonine kinase involved in cellular innate immunity, metabolism, and senescence. FK506-binding protein 12 (FKBP12) inhibits mTOR kinase activity via direct association. The FKBP12-mTOR association can be strengthened by the immunosuppressant rapamycin, but the underlying mechanism remains elusive. We show here that the FKBP12-mTOR association is tightly regulated by an acetylation-deacetylation cycle. FKBP12 is acetylated on the lysine cluster (K45/K48/K53) by CREB-binding protein (CBP) in mammalian cells in response to nutrient treatment. Acetyl-FKBP12 associates with CBP acetylated Rheb. Rapamycin recruits SIRT2 with a high affinity for FKBP12 association and deacetylation. SIRT2-deacetylated FKBP12 then switches its association from Rheb to mTOR. Nutrient-activated mTOR phosphorylates IRF3S386 for the antiviral response. In contrast, rapamycin strengthening FKBP12- mTOR association blocks mTOR antiviral activity by recruiting SIRT2 to deacetylate FKBP12. Hence, on/off mTOR activity in response to environmental nutrients relies on FKBP12 acetylation and deacetylation status in mammalian cells.
资助项目	National Natural Science Foundation of China[81820108023] ; National Natural Science Foundation of China[82030077] ; National Natural Science Foundation of China[2016YFC1302402] ; National Natural Science Foundation of China[2018YFC1705500] ; National Natural Science Foundation of China[81902977] ; Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
WOS关键词	MAMMALIAN TARGET ; DENDRITIC CELLS ; ACTIVATES MTOR ; PROTEIN-KINASE ; I INTERFERON ; COMPLEX ; ACETYLATION ; AUTOPHAGY ; RHEB ; INHIBITION
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	CELL PRESS
WOS记录号	WOS:000730069600008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/299241]
专题	中国科学院上海药物研究所
通讯作者	Deng, Wei; Luo, Cheng; Chin, Y. Eugene
作者单位	1.Soochow Univ, Inst Biol, 199 Renai Rd, Suzhou 215123, Jiangsu, Peoples R China 2.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 3.Chinese Acad Sci, Inst Biochem & Cell Biol, 320 Yueyang Rd, Shanghai 200031, Peoples R China 4.Chinese Acad Sci, Inst Nutr & Hlth Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China 5.Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA 6.Tsinghua Univ, Sch Med, Lab Membrane Biol, Beijing 100084, Peoples R China 7.Tsinghua Univ, Sch Pharmaceut Sci, Beijing 100084, Peoples R China 8.Soochow Univ, Hematol Ctr, Cyrus Tang Med Inst, 199 Renai Rd, Suzhou 215123, Jiangsu, Peoples R China
推荐引用方式 GB/T 7714	Hu, Lin,Chen, Fuxian,Wu, Chao,et al. Rapamycin recruits SIRT2 for FKBP12 deacetylation during mTOR activity modulation in innate immunity[J]. ISCIENCE,2021,24(11):22.
APA	Hu, Lin.,Chen, Fuxian.,Wu, Chao.,Wang, Jun.,Chen, Si-si.,...&Chin, Y. Eugene.(2021).Rapamycin recruits SIRT2 for FKBP12 deacetylation during mTOR activity modulation in innate immunity.ISCIENCE,24(11),22.
MLA	Hu, Lin,et al."Rapamycin recruits SIRT2 for FKBP12 deacetylation during mTOR activity modulation in innate immunity".ISCIENCE 24.11(2021):22.