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学科主题: 基础医学
题名:
ARF-dependent regulation of ATM and p53 associated KZNF (Apak) protein activity in response to oncogenic stress
作者: Wang, Shan1,2; Tian, Chunyan1; Xing, Guichun1; Gao, Mei1; Jiao, Wenjuan1; Xiao, Tingting1; Yin, Yuxin3; He, Fuchu1,4; Zhang, Lingqiang1
关键词: ATM and p53 associated KZNF protein ; ARF ; Oncogenic stress ; p53
刊名: FEBS LETTERS
发表日期: 2010-09-24
DOI: 10.1016/j.febslet.2010.08.015
卷: 584, 期:18, 页:3909-3915
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
关键词[WOS]: TUMOR-SUPPRESSOR ; DNA-DAMAGE ; P53-DEPENDENT APOPTOSIS ; MDM2 ; P19(ARF) ; PHOSPHORYLATION ; ACTIVATION ; PATHWAY ; LINKS
英文摘要:

The KRAB-type zinc-finger protein Apak (ATM and p53 associated KZNF protein) specifically suppresses p53-mediated apoptosis. Upon DNA damage, Apak is phosphorylated and inhibited by ATM kinase, resulting in p53 activation. However, how Apak is regulated in response to oncogenic stress remains unknown. Here we show that upon oncogene activation, Apak is inhibited in the tumor suppressor ARF-dependent but ATM-independent manner. Oncogene-induced ARF protein directly interacts with Apak and competes with p53 to bind to Apak, resulting in Apak dissociation from p53. Thus, Apak is differentially regulated in the ARF and ATM-dependent manner in response to oncogenic stress and DNA damage, respectively.

Structured summary:

MINT-7989670: p53 (uniprotkb:P04637) binds (MI:0407) to APAK (uniprotkb:Q8TAQ5) by pull down (MI:0096)

MINT-7989812: HDM2 (uniprotkb:Q00987) physically interacts (MI:0915) with ARF (uniprotkb:Q8N726-1) by anti bait coimmunoprecipitation (MI:0006)

MINT-7989603, MINT-7989626: APAK (uniprotkb:Q8TAQ5) physically interacts (MI:0915) with ARF (uniprotkb:Q8N726-1) by anti bait coimmunoprecipitation (MI:0006)

MINT-7989653: ARF (uniprotkb:Q8N726-1) binds (MI:0407) to APAK (uniprotkb:Q8TAQ5) by pull down (MI:0096)

MINT-7989686, MINT-7989705, MINT-7989747: APAK (uniprotkb:Q8TAQ5) physically interacts (MI:0915) with ARF (uniprotkb:Q8N726-1) by anti tag coimmunoprecipitation (MI:0007)

MINT-7989724: APAK (uniprotkb:Q8TAQ5) physically interacts (MI:0914) with ARF (uniprotkb:Q8N726-1) and p53 (uniprotkb:P04637) by anti tag coimmunoprecipitation (MI:0007)

MINT-7989635: ARF (uniprotkb:Q8N726-1) and APAK (uniprotkb:Q8TAQ5) colocalize (MI:0403) by fluorescence microscopy (MI:0416) MINT-7989584,

MINT-7989773: APAK (uniprotkb:Q8TAQ5) physically interacts (MI:0915) with p53 (uniprotkb: P04637) by anti tag coimmunoprecipitation (MI:0007) (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 2007CB914601 ; 2006CB910802 ; 2011CB910802 ; 2010CB912202 ; 30871373 ; 5102034 ; 2009ZX09503-002 ; 2009ZX09301-002 ; Y200802
项目资助者: Chinese National Basic Research Programs ; Chinese National Natural Science Foundation ; Beijing Natural Science Foundation ; National Key Technologies R& ; D Program for New Drugs ; State Key Laboratory of Proteomics
WOS记录号: WOS:000282187500014
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/50027
Appears in Collections:基础医学院_病理学系_期刊论文

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作者单位: 1.Beijing Proteome Res Ctr, Beijing Inst Radiat Med, State Key Lab Prote, Beijing 100850, Peoples R China
2.NW A&F Univ, Coll Anim Sci & Technol, Shaanxi Key Lab Mol Biol Agr, Yangling 712100, Shaanxi, Peoples R China
3.Peking Univ, Sch Basic Med Sci, Dept Pathol, Beijing 100191, Peoples R China
4.Tsinghua Univ, Dept Biol Sci & Biotechnol, Beijing 100084, Peoples R China

Recommended Citation:
Wang, Shan,Tian, Chunyan,Xing, Guichun,et al. ARF-dependent regulation of ATM and p53 associated KZNF (Apak) protein activity in response to oncogenic stress[J]. FEBS LETTERS,2010,584(18):3909-3915.
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