@article{7c6bcf60bd9b425f8145af7e9906fa32,
title = "USP37 promotes deubiquitination of HIF2α in kidney cancer",
abstract = "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.",
keywords = "CcRCC, Deubiquitination, HIF2α, USP37",
author = "Kai Hong and Lianxin Hu and Xijuan Liu and Simon, {Jeremy M.} and Ptacek, {Travis S.} and Xingnan Zheng and Chengheng Liao and Baldwin, {Albert S.} and Qing Zhang",
note = "Funding Information: We thank the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center Tissue Procurement Facility and UNC Animal Studies Core for excellent help. This work was supported in part by the 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). Q.Z. is an American Cancer Society Research Scholar, CPRIT Scholar in Cancer Research, V Scholar, Kimmel Scholar, Susan G. Komen Career Catalyst awardee, and Mary Kay Foundation awardee. Q.Z. is also supported by the Kidney Cancer Research Alliance (KCCure). Funding Information: ACKNOWLEDGMENTS. We thank the University of North Carolina (UNC) Lineberger Comprehensive Cancer Center Tissue Procurement Facility and UNC Animal Studies Core for excellent help. This work was supported in part by the 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). Q.Z. is an American Cancer Society Research Scholar, CPRIT Scholar in Cancer Research, V Scholar, Kimmel Scholar, Susan G. Komen Career Catalyst awardee, and Mary Kay Foundation awardee. Q.Z. is also supported by the Kidney Cancer Research Alliance (KCCure).",
year = "2020",
month = jun,
day = "9",
doi = "10.1073/pnas.2002567117",
language = "English (US)",
volume = "117",
pages = "13023--13032",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "23",
}