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USP3 promotes breast cancer cell proliferation by deubiquitinating KLF5

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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 650223, China [2]University of the Chinese Academy of Sciences, Beijing 101407, China [3]First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China [4]Department of Breast Surgery, Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650118, China [5]Cancer Epigenetics Laboratory, Department of Clinical Oncology, Sir Y. K. Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, Shenzhen Research Institute, Chinese University of Hong Kong, Hong Kong 518172, China [6]Kunming Institute of Zoology–Chinese University of Hong Kong Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology [7]Institute of Stem Cell and Reproductive Biology, Chinese Academy of Sciences, Beijing 100101, China
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The Krüppel-like factor 5 (KLF5) transcription factor is highly expressed in basal type breast cancer and promotes breast cancer cell proliferation, survival, migration, and tumorigenesis. KLF5 protein stability is regulated by ubiquitination. In this study, ubiquitin-specific protease 3 (USP3) was identified as a new KLF5 deubiquitinase by genome-wide siRNA library screening.Wedemonstrated that USP3 interacts with KLF5 and stabilizes KLF5 via deubiquitination. USP3 knockdown inhibits breast cancer cell proliferation in vitro and tumorigenesis in vivo, which can be partially rescued by ectopic expression of KLF5. Furthermore, we observed a positive correlation between USP3 and KLF5 protein expression levels in human breast cancer samples. These findings suggest that USP3 is a new KLF5 deubiquitinase and that USP3 may represent a potential therapeutic target for breast cancer.

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出版当年[2020]版:
大类 | 2 区 生物
小类 | 3 区 生化与分子生物学
最新[2023]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
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出版当年[2019]版:
Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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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 650223, China [2]University of the Chinese Academy of Sciences, Beijing 101407, China [3]First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China
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