ARF-dependent regulation of ATM and p53 associated KZNF (Apak) protein activity in response to oncogenic stress

被引：17
|
作者：
Wang, Shan [1 ,2 ]
Tian, Chunyan [1 ]
Xing, Guichun [1 ]
Gao, Mei [1 ]
Jiao, Wenjuan [1 ]
Xiao, Tingting [1 ]
Yin, Yuxin [3 ]
He, Fuchu [1 ,4 ]
Zhang, Lingqiang [1 ]
机构：
[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
来源：
FEBS LETTERS | 2010年 / 584卷 / 18期
基金：
北京市自然科学基金;
关键词：
ATM and p53 associated KZNF protein; ARF; Oncogenic stress; p53; TUMOR-SUPPRESSOR; DNA-DAMAGE; P53-DEPENDENT APOPTOSIS; MDM2; P19(ARF); PHOSPHORYLATION; ACTIVATION; PATHWAY; LINKS;
D O I：
10.1016/j.febslet.2010.08.015
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
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.
引用
收藏
页码：3909 / 3915
页数：7
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