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; Wenlin Chen; Junying Qin; Zhongmei Zhou; Rong Liu; Linlin Liu; Jing Tan; Tianning Zou; Hongyuan Li; Guosheng Ren; Ceshi Chen

doi:10.18632/oncotarget.4128

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Research Papers:

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, Wenlin Chen, Junying Qin, Zhongmei Zhou, Rong Liu, Linlin Liu, Jing Tan, Tianning Zou, Hongyuan Li, Guosheng Ren and Ceshi Chen _

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Oncotarget. 2015; 6:21369-21378. https://doi.org/10.18632/oncotarget.4128

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Abstract

Fei Ge1,2,*, Wenlin Chen3,*, Junying Qin1,*, Zhongmei Zhou1, Rong Liu1, Linlin Liu4, Jing Tan3, Tianning Zou3, Hongyuan Li2, Guosheng Ren2 and Ceshi Chen1

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, 2015Published: May 12, 2015

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.

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Research Papers:

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