中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Rapamycin recruits SIRT2 for FKBP12 deacetylation during mTOR activity modulation in innate immunity

文献类型：期刊论文

作者Hu, Lin1; Chen, Fuxian1; Wu, Chao1; Wang, Jun2; Chen, Si-si3,4; Li, Xiang-rong1; Wang, Jing1; Wu, Linpeng1; Ding, Jian-ping3,4; Wang, Jian-chuan5
刊名ISCIENCE
出版日期2021-11-19
卷号24期号:11页码:22
DOI10.1016/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.
WOS关键词MAMMALIAN TARGET ; DENDRITIC CELLS ; ACTIVATES MTOR ; PROTEIN-KINASE ; I INTERFERON ; COMPLEX ; ACETYLATION ; AUTOPHAGY ; RHEB ; INHIBITION
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研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000730069600008
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/299241]  
专题新药研究国家重点实验室
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.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。