机构：[1]Department of Hematology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.[2]Guangdong and Guangzhou Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, P. R. China.[3]Department of Pharmacology, Soochow University, Jiangsu 215123, P. R. China.[4]Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China深圳市中医院深圳医学信息中心
Chronic myelogenous leukemia (CML) is a clonal malignancy of hematopoietic stem cells featured with the fusion protein kinase BCR-ABL. To elicit the mechanism underlying BCR-ABL stability, we perform a screen against a panel of deubiquitinating enzymes (DUBs) and find that the ubiquitin-specific protease 7 (USP7) drastically stabilizes the BCR-ABL fusion protein. Further studies show that USP7 interacts with BCR-ABL and blocks its polyubiquitination and degradation. Moreover, USP7 knockdown triggers BCR-ABL degradation and suppresses its downstream signaling transduction. In line with this finding, genetic or chemical inhibition of USP7 leads to BCR-ABL protein degradation, suppresses BCR/ABL signaling, and induces CML cell apoptosis. Furthermore, we find the antimalarial artesunate (ART) significantly inhibits USP7/BCR-ABL interaction, thereby promoting BCR-ABL degradation and inducing CML cell death. This study thus identifies USP7 as a putative Dub of BCR-ABL and provides a rationale in targeting USP7/BCR-ABL for the treatment of CML.
基金：
This work was partly supported by the National Natural Science Foundation of
China (#81770154 and #81970194 to X.M. and #81770215 to B.C.), Natural
Science Foundation Research Team of Guangdong Province (2018B030312001
to J.L. and H.H.), by Suzhou Municipal Science and Technology Project
(#SYS201702 to B.C.), and by Guangzhou Municipal Science and Technology
Project (#202002030059 to X.M.). X.M. is a Nanshan Scholar of Guangzhou
Medical University.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|2 区生物
小类|2 区细胞生物学
最新[2025]版：
大类|1 区生物学
小类|2 区细胞生物学
第一作者：
第一作者机构：[1]Department of Hematology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.[2]Guangdong and Guangzhou Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, P. R. China.[3]Department of Pharmacology, Soochow University, Jiangsu 215123, P. R. China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Hematology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.[2]Guangdong and Guangzhou Key Laboratory of Protein Modification and Degradation, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou 511436, P. R. China.[3]Department of Pharmacology, Soochow University, Jiangsu 215123, P. R. China.[4]Institute of Clinical Pharmacology, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
推荐引用方式(GB/T 7714)：
Shuoyi Jiang,Xiaoge Wang,Yuanming He,et al.Suppression of USP7 induces BCR-ABL degradation and chronic myelogenous leukemia cell apoptosis.[J].Cell death & disease.2021,12(5):456.doi:10.1038/s41419-021-03732-6.
APA：
Shuoyi Jiang,Xiaoge Wang,Yuanming He,Hongbiao Huang,Biyin Cao...&Xinliang Mao.(2021).Suppression of USP7 induces BCR-ABL degradation and chronic myelogenous leukemia cell apoptosis..Cell death & disease,12,(5)
MLA：
Shuoyi Jiang,et al."Suppression of USP7 induces BCR-ABL degradation and chronic myelogenous leukemia cell apoptosis.".Cell death & disease 12..5(2021):456
生物学