单位：[1]Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei Province, China.华中科技大学同济医学院附属同济医院超声影像科[2]Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599.[3]Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390.[4]Department of Genetics, Neuroscience Center, University of North Carolina, Chapel Hill, NC 27599.[5]UNC Neuroscience Center, Carolina Institute for Developmental Disabilities, University of North Carolina, Chapel Hill, NC 27599
Clear cell renal cell carcinoma (ccRCC) is characterized by loss of tumor suppressor Von Hippel Lindau (VHL) function, which leads to accumulation of hypoxia inducible factor α (including HIF1α and HIF2α). HIF2α was previously reported to be one of the major oncogenic drivers in ccRCC, however, its therapeutic targets remain challenging. Here we performed a deubiquitinase (DUB) complementary DNA (cDNA) library binding screen and discovered that ubiquitin-specific peptidase 37 (USP37) is a DUB that binds HIF2α and promotes HIF2α deubiquitination. As a result, USP37 promotes HIF2α protein stability in an enzymatically dependent manner, and depletion of USP37 leads to HIF2α down-regulation in ccRCC. Functionally, USP37 depletion causes decreased cell proliferation measured by MTS, two-dimensional (2D) colony formation as well as three-dimensional (3D) anchorage- independent growth. USP37 is also essential for maintaining kidney tumorigenesis in an orthotopic xenograft model and its depletion leads to both decreased primary kidney tumorigenesis and spontaneous lung metastasis. Our results suggest that USP37 is a potential therapeutic target in ccRCC.
基金：
National Cancer Institute (Q.Z., R01CA211732 and R21CA223675) and
Cancer Prevention and Research Institute of Texas (CPRIT, RR190058 to Q.Z.).
J.M.S. and T.S.P. were supported by The Eunice Kennedy Shriver National
Institute of Child Health and Human Development (U54HD079124) and
the National Institute of Neurological Disorders and Stroke (NINDS)
(P30NS045892).
第一作者单位：[1]Department of Medical Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, Hubei Province, China.[2]Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Hong Kai,Hu Lianxin,Liu Xijuan,et al.USP37 promotes deubiquitination of HIF2α in kidney cancer.[J].Proceedings Of The National Academy Of Sciences Of The United States Of America.2020,117(23):13023-13032.doi:10.1073/pnas.2002567117.
APA：
Hong Kai,Hu Lianxin,Liu Xijuan,Simon Jeremy M,Ptacek Travis S...&Zhang Qing.(2020).USP37 promotes deubiquitination of HIF2α in kidney cancer..Proceedings Of The National Academy Of Sciences Of The United States Of America,117,(23)
MLA：
Hong Kai,et al."USP37 promotes deubiquitination of HIF2α in kidney cancer.".Proceedings Of The National Academy Of Sciences Of The United States Of America 117..23(2020):13023-13032
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