Ataxin-3 like (ATXN3L), a member of the Josephin family of deubiquitinating enzymes, promotes breast cancer proliferation by deubiquitinating Kruppel-like factor 5 (KLF5)
机构:[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重庆医科大学附属第一医院[3]Department of Breast Surgery, The 3rd Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China[4]Laboratory for Conservation and Utilization of Bio-resource, Yunnan University, Kunming, China
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 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.
基金:
National Key
Basic Research Program of China (2013CB910900),
the Strategic Priority Research Program of the Chinese
Academy of Sciences, Stem Cell and Regenerative
Medicine Research (XDA01040406), and the National
Natural Science Foundation of China (81120108019,
81325016, U1132605, and 31260208).
第一作者机构:[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
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
Fei Ge,Wenlin Chen,Junying Qin,et al.Ataxin-3 like (ATXN3L), a member of the Josephin family of deubiquitinating enzymes, promotes breast cancer proliferation by deubiquitinating Kruppel-like factor 5 (KLF5)[J].ONCOTARGET.2015,6(25):21369-21378.doi:10.18632/oncotarget.4128.
APA:
Fei Ge,Wenlin Chen,Junying Qin,Zhongmei Zhou,Rong Liu...&Ceshi Chen.(2015).Ataxin-3 like (ATXN3L), a member of the Josephin family of deubiquitinating enzymes, promotes breast cancer proliferation by deubiquitinating Kruppel-like factor 5 (KLF5).ONCOTARGET,6,(25)
MLA:
Fei Ge,et al."Ataxin-3 like (ATXN3L), a member of the Josephin family of deubiquitinating enzymes, promotes breast cancer proliferation by deubiquitinating Kruppel-like factor 5 (KLF5)".ONCOTARGET 6..25(2015):21369-21378