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学科主题: 基础医学
题名:
HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin-proteasome pathway
作者: Wang, Xiaozhen1,2; Lu, Guang1; Li, Li1; Yi, Juan1; Yan, Kaowen1; Wang, Yaqing1; Zhu, Baili1; Kuang, Jingyu1; Lin, Ming1; Zhang, Sha1; Shao, Genze1,2
关键词: HUWE1 ; BRCA1 ; Ubiquitination ; Degradation
刊名: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
发表日期: 2014-02-14
DOI: 10.1016/j.bbrc.2013.12.053
卷: 444, 期:3, 页:290-295
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics
关键词[WOS]: DNA-DAMAGE ; POLYUBIQUITIN CHAINS ; TUMOR-SUPPRESSOR ; SPORADIC BREAST ; OVARIAN-CANCER ; LIGASE ; PROTEIN ; REPAIR ; CELLS ; PROLIFERATION
英文摘要:

The cellular BRCA1 protein level is essential for its tumor suppression activity and is tightly regulated through multiple mechanisms including ubiquitn-proteasome system. E3 ligases are involved to promote BRCA1 for ubiquitination and degradation. Here, we identified HUWE1/Mule/ARF-BP1 as a novel BRCA1-interacting protein involved in the control of BRCA1 protein level. HUWE1 binds BRCA1 through its N-terminus degron domain. Depletion of HUWE1 by siRNA-mediated interference significantly increases BRCA1 protein levels and prolongs the half-life of BRCA1. Moreover, exogenous expression of HUWE1 promotes BRCA1 degradation through the ubiquitin-proteasome pathway, which could explain an inverse correlation between HUWE1 and BRCA1 levels in MCF10F, MCF7 and MDA-MB-231 breast cancer cells. Consistent with a functional role for HUWE1 in regulating BRCA1 -mediated cellular response to DNA damage, depletion of HUWE1 by siRNA confers increased resistance to ionizing radiation and mitomycin. These data indicate that HUWE1 is a critical negative regulator of BRCA1 and suggest a new molecular mechanism for breast cancer pathogenesis. (C) 2014 published by Elsevier Inc.

语种: 英语
所属项目编号: 81272915 ; 7122099 ; 20110001110013 ; JWSL44-8
项目资助者: National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Doctoral Program of Higher Education ; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry ; 985 Program, Ministry of Education of China
WOS记录号: WOS:000332139200002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54130
Appears in Collections:基础医学院_细胞生物学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Dept Cell Biol, Beijing 100191, Peoples R China
2.Peking Univ, Inst Syst Biol, Beijing 100191, Peoples R China

Recommended Citation:
Wang, Xiaozhen,Lu, Guang,Li, Li,et al. HUWE1 interacts with BRCA1 and promotes its degradation in the ubiquitin-proteasome pathway[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2014,444(3):290-295.
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