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Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T-cell Leukemogenesis
Jiang, Jue1,2,13; Wang, Jingchao1,2,13; Yue, Ming3,13; Cai, Xiaolian4; Wang, Tianci2; Wu, Chao2; Su, Hexiu2; Wang, Yanwu5; Han, Meng6; Zhang, Yingchi7,8,9; Zhu, Xiaofan7,8,9; Jiang, Peng10; Li, Peng11; Sun, Yonghua12; Xiao, Wuhan; Feng, Hui12; Qing, Guoliang1,2; Liu, Hudan1,2
Corresponding AuthorLiu, Hudan(hudanliu@whu.edu.cn)
2020-02-10
Source PublicationCANCER CELL
ISSN1535-6108
Volume37Issue:2Pages:200-+
AbstractDeregulation of MYC plays an essential role in T cell acute lymphoblastic leukemia (T-ALL), yet the mechanisms underlying its deregulation remain elusive. Herein, we identify a molecular mechanism responsible for reciprocal activation between Aurora B kinase (AURKB) and MYC. AURKB directly phosphorylates MYC at serine 67, counteracting GSK3b-directed threonine 58 phosphorylation and subsequent FBXW7-mediated proteasomal degradation. Stabilized MYC, in concert with T cell acute lymphoblastic leukemia 1 (TAL1), directly activates AURKB transcription, constituting a positive feedforward loop that reinforces MYC-regulated oncogenic programs. Therefore, inhibitors of AURKB induce prominent MYC degradation concomitant with robust leukemia cell death. These findings reveal an AURKB-MYC regulatory circuit that underlies T cell leukemogenesis, and provide a rationale for therapeutic targeting of oncogenic MYC via AURKB inhibition.
DOI10.1016/j.ccell.2020.01.001
Funding OrganizationNational Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; American Cancer Society ; American Cancer Society ; American Cancer Society ; American Cancer Society ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; American Cancer Society ; American Cancer Society ; American Cancer Society ; American Cancer Society ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; American Cancer Society ; American Cancer Society ; American Cancer Society ; American Cancer Society ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; American Cancer Society ; American Cancer Society ; American Cancer Society ; American Cancer Society
Indexed BySCI ; SCI
Language英语
Funding ProjectNational Key R&D Program of China[2017YFA0505600] ; National Natural Science Foundation of China[81970152] ; National Natural Science Foundation of China[81770177] ; National Natural Science Foundation of China[81830084] ; National Natural Science Foundation of China[81803003] ; National Science Foundation for Distinguished Young Scholar[81725013] ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars[2017CFA072] ; Hubei Provincial Natural Science Fund for Creative Research Groups[2018CFA018] ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University[TFJC2018005] ; National Institutes of Health[CA215059] ; American Cancer Society[RSG-17-204-01-TBG]
WOS Research AreaOncology ; Cell Biology
WOS SubjectOncology ; Cell Biology
WOS IDWOS:000513775300010
WOS KeywordC-MYC ; ONCOGENIC TRANSFORMATION ; TUMOR-SUPPRESSOR ; N-MYC ; ACTIVATION ; EXPRESSION ; LEUKEMIA ; PATHWAY ; COMPLEX ; NOTCH1
PublisherCELL PRESS
Funding OrganizationNational Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; American Cancer Society ; American Cancer Society ; American Cancer Society ; American Cancer Society ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; American Cancer Society ; American Cancer Society ; American Cancer Society ; American Cancer Society ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; American Cancer Society ; American Cancer Society ; American Cancer Society ; American Cancer Society ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Key R&D Program of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Natural Science Foundation of China ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; National Science Foundation for Distinguished Young Scholar ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Distinguished Young Scholars ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Hubei Provincial Natural Science Fund for Creative Research Groups ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; National Institutes of Health ; American Cancer Society ; American Cancer Society ; American Cancer Society ; American Cancer Society
Citation statistics
Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/35001
Collection其他_期刊论文
Corresponding AuthorLiu, Hudan
Affiliation1.Wuhan Univ, Zhongnan Hosp, Dept Hematol, Wuhan 430071, Peoples R China
2.Wuhan Univ, Med Res Inst, Frontier Sci Ctr Immunol & Metab, Wuhan 430071, Peoples R China
3.Huazhong Univ Sci & Technol, Tongji Med Coll, Cent Hosp Wuhan, Dept Pharm, Wuhan 430014, Peoples R China
4.Chinese Acad Sci, Innovat Acad Seed Design, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
5.Wuhan Univ, Sch Basic Med Sci, Dept Histol & Embryol, Wuhan 430071, Peoples R China
6.Tsinghua Univ, Sch Life Sci, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China
7.Chinese Acad Med Sci, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China
8.Chinese Acad Med Sci, Div Pediat, Blood Dis Ctr, Inst Hematol & Blood Dis Hosp, Tianjin 300020, Peoples R China
9.Peking Union Med Coll, Tianjin 300020, Peoples R China
10.Tsinghua Univ, Sch Life Sci, Collaborat Innovat Ctr Canc Med, Beijing 100084, Peoples R China
11.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, South China Inst Stem Cell Biol & Regenerat Med, Guangzhou 510530, Peoples R China
12.Boston Univ, Sch Med, Dept Pharmacol, Canc Res Ctr,Sect Hematol & Med Oncol, Boston, MA 02118 USA
13.Boston Univ, Sch Med, Dept Med, Canc Res Ctr,Sect Hematol & Med Oncol, Boston, MA 02118 USA
Recommended Citation
GB/T 7714
Jiang, Jue,Wang, Jingchao,Yue, Ming,et al. Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T-cell Leukemogenesis[J]. CANCER CELL,2020,37(2):200-+.
APA Jiang, Jue.,Wang, Jingchao.,Yue, Ming.,Cai, Xiaolian.,Wang, Tianci.,...&Liu, Hudan.(2020).Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T-cell Leukemogenesis.CANCER CELL,37(2),200-+.
MLA Jiang, Jue,et al."Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T-cell Leukemogenesis".CANCER CELL 37.2(2020):200-+.
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