机构：[1]Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China[2]Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China[3]Department of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine[4]Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.Synthetic Biology and Biotechnology Laboratory, State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China[5]Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China[6]Centre for Reproductive Medicine, Shanghai Jiao Tong University Affiliated Sixth People Hospital, Shanghai 200233, China[7]Taishan Immunology Program, Binzhou Medical University, Yantai 264003, China[8]Department of Physiology, UT Southwestern Medical Center, Dallas, TX 75390, USA
In addition to acting as building blocks for biosynthesis, aminoacidsmight serve as signalingregulators in various physiological and pathological processes. However, it remains unknown whether amino acid levels affect the activities of hematopoietic stem cells (HSCs). By using a genetically encoded fluorescent sensor of the intracellular levels of branched-chain amino acids (BCAAs), we couldmonitor the dynamics of BCAA metabolism in HSCs. A mitochondrial-targeted 2C-type Ser/Thr protein phosphatase (PPM1K) promotes the catabolism of BCAAs to maintain MEIS1 and p21 levels by decreasing the ubiquitination-mediated degradation controlled by the E3 ubiquitin ligase CDC20. PPM1K deficiency led to a notable decrease in MEIS1/p21 signaling to reduce the glycolysis and quiescence of HSCs, followed by a severe impairment in repopulation activities. Moreover, the deletion of Ppm1k dramatically extended survival in amurine leukemia model. These findings will enhance the current understanding of nutrient signaling in metabolism and function of stem cells.
基金：
National Natural Science Foundation
of China (81422001, 81570093, 81721004, 81471524, 30971094, 81270317,
81570717, and 81522011), and its innovative group (No. 81721004), the 1000-
Youth Elite Program, National Basic Research Program of China (973Program,
2014CB965000, and NO2015CB910403), the NIH (1R01CA172268), CPRIT
RP140402, Taishan Scholar Immunology Program, Ministry of Science and
Technology of China (2012BAI02B05 and 2013YQ030923), Science and Technology
Commission of Shanghai Municipality (14411968300, 13ZR1423300,
16JC1404400, and 17DZ2260100), and Natural Science Foundation of
Shanghai (17ZR1415500).
第一作者机构：[1]Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China[2]Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China[3]Department of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine
共同第一作者：
通讯作者：
通讯机构：[1]Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China[2]Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai 200031, China[3]Department of Ophthalmology, Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine
推荐引用方式(GB/T 7714)：
Liu Xiaoye,Zhang Feifei,Zhang Yaping,et al.PPM1K Regulates Hematopoiesis and Leukemogenesis through CDC20-Mediated Ubiquitination of MEIS1 and p21[J].CELL REPORTS.2018,23(5):1461-1475.doi:10.1016/j.celrep.2018.03.140.
APA：
Liu, Xiaoye,Zhang, Feifei,Zhang, Yaping,Li, Xie,Chen, Chiqi...&Zheng, Junke.(2018).PPM1K Regulates Hematopoiesis and Leukemogenesis through CDC20-Mediated Ubiquitination of MEIS1 and p21.CELL REPORTS,23,(5)
MLA：
Liu, Xiaoye,et al."PPM1K Regulates Hematopoiesis and Leukemogenesis through CDC20-Mediated Ubiquitination of MEIS1 and p21".CELL REPORTS 23..5(2018):1461-1475
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