Ataxin-3 Like (ATXN3L), a Member of the Josephin Family of Deubiquitinating Enzymes, Promotes Breast Cancer Proliferation by Deubiquitinating Krüppel-like Factor 5 (KLF5)

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Jun 17

PMID 26079537

Citations 28

Authors

Fei Ge

Wenlin Chen

Junying Qin

Zhongmei Zhou

Rong Liu

Linlin Liu

Jing Tan

Tianning Zou

Hongyuan Li

Guosheng Ren

Ceshi Chen

Affiliations

Soon will be listed here.

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.

Citing Articles

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