title: Ataxin-3 like (ATXN3L), a member of the Josephin family of deubiquitinating enzymes, promotes breast cancer proliferation by deubiquitinating Krüppel-like factor 5 (KLF5).
abstract: The Krüppel-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 SCFFbw7, 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.
authors.affiliation: 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.|Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Ge
authors.affiliation: Department of Breast Surgery, The 3rd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Chen
authors.affiliation: 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.
authors.forename: Junying
authors.initials: J
authors.lastname: Qin
authors.affiliation: 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.
authors.forename: Zhongmei
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.affiliation: Laboratory for Conservation and Utilization of Bioresource, Yunnan University, Kunming, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Breast Surgery, The 3rd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Tan
authors.affiliation: Department of Breast Surgery, The 3rd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
authors.forename: Tianning
authors.initials: T
authors.lastname: Zou
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Hongyuan
authors.initials: H
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
authors.affiliation: 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.
authors.forename: Ceshi
authors.initials: C
authors.lastname: Chen
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D057809:HEK293 Cells; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D025941:Protein Interaction Mapping; D034741:RNA, Small Interfering / Q000378:metabolism; D064570:Ubiquitin-Specific Proteases / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; D010450:Endopeptidases; C556818:ATXN3L protein, human; D064570:Ubiquitin-Specific Proteases
keywords: ATXN3L; DUB; KLF5; breast cancer