Ataxin-3 like (ATXN3L), a member of the Josephin family of deubiquitinating enzymes, promotes breast cancer proliferation by deubiquitinating Krüppel-like factor 5 (KLF5)

// Fei Ge 1,2,* , Wenlin Chen 3,* , Junying Qin 1,* , Zhongmei Zhou 1 , Rong Liu 1 , Linlin Liu 4 , Jing Tan 3 , Tianning Zou 3 , Hongyuan Li 2 , Guosheng Ren 2 and Ceshi Chen 1 1 Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China 2 Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China 3 Department of Breast Surgery, The 3rd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China 4 Laboratory for Conservation and Utilization of Bioresource, Yunnan University, Kunming, China * These authors contributed equally to this work Correspondence to: Ceshi Chen, email: // Guosheng Ren, email: // Keywords : ATXN3L; KLF5; DUB; breast cancer Received : February 02, 2015 Accepted : May 02, 2015 Published : May 12, 2015 Abstract The Kruppel-like factor 5 (KLF5) has been suggested to promote breast cell proliferation, survival and tumorigenesis. KLF5 protein degradation is increased by several E3 ubiquitin ligases, including WWP1 and SCF Fbw7 , through the ubiquitin-proteasome pathway. However, the deubiquitinase (DUB) of KLF5 has not been demonstrated. In this study, we identified ATXN3L as a KLF5 DUB by genome-wide siRNA screening. ATXN3L directly binds to KLF5, decreasing its ubiquitination and thus degradation. Functionally, knockdown of ATXN3L inhibits breast cancer cell proliferation partially through KLF5. These findings reveal a previously unrecognized role of ATXN3L in the regulation of KLF5 stability in breast cancer. ATXN3L might be a therapeutic target for breast cancer.