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Identification of XAF1 as an endogenous AKT inhibitor

文献类型：期刊论文

作者Chen, Min1; Wang, Kangjunjie1,2; Han, Ying3,4; Yan, Shukun3,5; Yuan, Huairui4; Liu, Qiuli6; Li, Long; Li, Ni4; Zhu, Hongwen7,8; Lu, Dayun3,7,8
刊名CELL REPORTS
出版日期2023-07-25
卷号42期号:7页码:25
ISSN号2211-1247
DOI10.1016/j.celrep.2023.112690
通讯作者Chen, Yong(yongchen@sibcb.ac.cn) ; Qin, Jun(qinjun@sibs.ac.cn) ; Gao, Daming(dgao@sibcb.ac.cn)
英文摘要AKT kinase is a key regulator in cell metabolism and survival, and its activation is strictly modulated. Herein, we identify XAF1 (XIAP-associated factor) as a direct interacting protein of AKT1, which strongly binds the N-terminal region of AKT1 to block its K63-linked poly-ubiquitination and subsequent activation. Consistently, Xaf1 knockout causes AKT activation in mouse muscle and fat tissues and reduces body weight gain and insulin resistance induced by high-fat diet. Pathologically, XAF1 expression is low and anti -correlated with the phosphorylated p-T308-AKT signal in prostate cancer samples, and Xaf1 knockout stimulates the p-T308-AKT signal to accelerate spontaneous prostate tumorigenesis in mice with Pten heterozygous loss. And ectopic expression of wild-type XAF1, but not the cancer-derived P277L mutant, inhibits orthotopic tumorigenesis. We further identify Forkhead box O 1 (FOXO1) as a transcriptional regulator of XAF1, thus forming a negative feedback loop between AKT1 and XAF1. These results reveal an important intrinsic regulatory mechanism of AKT signaling.
WOS关键词X-LINKED INHIBITOR ; PROTEIN-KINASE B ; HEPATIC GLUCONEOGENESIS ; PI3K/AKT PATHWAY ; PROSTATE-CANCER ; PHOSPHORYLATION ; ACTIVATION ; EXPRESSION ; SKP2 ; GENE
资助项目National Key Research and Development Program of China[2020YFA0803203] ; National Key Research and Development Program of China[2019YFA0802102] ; National Natural Science Foundation of China[81925029] ; National Natural Science Foundation of China[81790253] ; National Natural Science Foundation of China[82230098] ; National Natural Science Foundation of China[32221002] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19020203] ; CAS project for young scientists in basic research[YSBR-014] ; Shanghai Municipal Science and Technology Major Project
WOS研究方向Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:001033675200001
源URL[http://119.78.100.183/handle/2S10ELR8/306803]  
专题中国科学院上海药物研究所
通讯作者Chen, Yong; Qin, Jun; Gao, Daming
作者单位1.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Cell Biol, CAS Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China
2.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Key Lab Syst Hlth Sci Zhejiang Prov, Hangzhou 310024, Peoples R China
3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Ctr Excellence Mol Cell Sci, CAS Key Lab Tissue Microenvironm & Tumor, 320 Yueyang Rd, Shanghai 200031, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai, State Key Lab Mol Biol,Ctr Excellence Mol Cell Sci, 333 Haike Rd, Shanghai 201210, Peoples R China
6.Army Med Univ, Daping Hosp, Inst Surg Res, Dept Urol, Chongqing 400042, Peoples R China
7.Chinese Acad Sci, Dept Analyt Chem, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
8.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
9.Fudan Univ, Dept Colorectal Surg, Shanghai Canc Ctr, Shanghai 200032, Peoples R China
10.East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Min,Wang, Kangjunjie,Han, Ying,et al. Identification of XAF1 as an endogenous AKT inhibitor[J]. CELL REPORTS,2023,42(7):25.
APA Chen, Min.,Wang, Kangjunjie.,Han, Ying.,Yan, Shukun.,Yuan, Huairui.,...&Gao, Daming.(2023).Identification of XAF1 as an endogenous AKT inhibitor.CELL REPORTS,42(7),25.
MLA Chen, Min,et al."Identification of XAF1 as an endogenous AKT inhibitor".CELL REPORTS 42.7(2023):25.

入库方式： OAI收割

来源：上海药物研究所

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