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Zinc ions activate AKT and promote prostate cancer cell proliferation via disrupting AKT intramolecular interaction

文献类型：期刊论文

作者Wang, Kangjunjie9,10; Chen, Min8; Yan, Shukun6,7; Han, Ying5; Yuan, Huairui7,9; Liu, Qiuli4; Lu, Dayun2,3; Li, Long9; Wang, Kaihua9; Liu, Fen7,9
刊名ONCOGENE
出版日期2024-10-23
页码11
ISSN号0950-9232
DOI10.1038/s41388-024-03195-x
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Prostate is a zinc rich organ and the physiological function of the abundant zinc ions is relatively less understood. AKT kinase is a pivotal regulator downstream of cytokines, growth factors and other extracellular stimuli, and the attachment of its PH domain to PtdIns-3,4,5-P3 (PIP3) and the subsequent phosphorylation of its kinase domain by PDPK1 are considered important for its activation. Herein, we report a regulatory mechanism of AKT kinase by zinc ions. Mechanistically, zinc ions directly bind to AKT and facilitate AKT activation through disrupting the interaction between PH and kinase domains within AKT molecule. Consistently, AKT1-H89A/E91A mutant (zinc-binding-deficient) fails to respond to zinc ions and exhibits strong interaction between PH and kinase domains, and it is less oncogenic in orthotopic xenograft model of prostate cancer. On the other hand, the AKT1-W80L mutant with minimum intra-molecular interaction between PH and kinase domains shows strong tumor promoting capacity although it could not be further stimulated by zinc ions. Overall, this study reveals a distinctive regulatory mechanism of AKT activation and implies a tumor promoting role of the zinc ions in prostate cancer.
WOS关键词PROTEIN-KINASE-B ; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE ; TRANSPORTERS ; BINDING ; AKT/PKB ; INSULIN ; DOMAIN
资助项目National Natural Science Foundation of China (National Science Foundation of China)
WOS研究方向Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
语种英语
WOS记录号WOS:001338083000001
出版者SPRINGERNATURE
源URL[http://119.78.100.183/handle/2S10ELR8/314005]  
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.Fudan Univ, Shanghai Canc Ctr, Dept Colorectal Surg, Shanghai 200032, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Dept Analyt Chem, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China
4.Army Med Univ, Daping Hosp, Inst Surg Res, Dept Urol, Chongqing 400042, Peoples R China
5.Chinese Acad Sci, CAS Key Lab Tissue Microenvironm & Tumor, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Nutr & Hlth Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci, Key Lab Epigenet Regulat & Intervent, Shanghai 200031, Peoples R China
7.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
8.Chinese Acad Sci, Interdisciplinary Res Ctr Biol & Chem, Shanghai Inst Organ Chem, Shanghai 201203, Peoples R China
9.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci, Key Lab Multicell Syst, Shanghai 200031, Peoples R China
10.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Key Lab Syst Hlth Sci Zhejiang Prov, Hangzhou 310024, Peoples R China
推荐引用方式
GB/T 7714		 Wang, Kangjunjie,Chen, Min,Yan, Shukun,et al. Zinc ions activate AKT and promote prostate cancer cell proliferation via disrupting AKT intramolecular interaction[J]. ONCOGENE,2024:11.
APA Wang, Kangjunjie.,Chen, Min.,Yan, Shukun.,Han, Ying.,Yuan, Huairui.,...&Gao, Daming.(2024).Zinc ions activate AKT and promote prostate cancer cell proliferation via disrupting AKT intramolecular interaction.ONCOGENE,11.
MLA Wang, Kangjunjie,et al."Zinc ions activate AKT and promote prostate cancer cell proliferation via disrupting AKT intramolecular interaction".ONCOGENE (2024):11.

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来源：上海药物研究所

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