GSTDTAP  > 资源环境科学
DOI10.1038/s41467-018-03865-x
A signature motif in LIM proteins mediates binding to checkpoint proteins and increases tumour radiosensitivity
Xu, Xiaojie1,2; Fan, Zhongyi1,3; Liang, Chaoyang1,4; Li, Ling1; Wang, Lili5; Liang, Yingchun1; Wu, Jun6; Chang, Shaohong6; Yan, Zhifeng7; Lv, Zhaohui8; Fu, Jing8; Liu, Yang9; Jin, Shuai9; Wang, Tao10; Hong, Tian1; Dong, Yishan11; Ding, Lihua1; Cheng, Long1; Liu, Rui12; Fu, Shenbo12; Jiao, Shunchang3; Ye, Qinong1,2
2017-01-17
发表期刊NATURE COMMUNICATIONS
ISSN2041-1723
出版年2017
卷号8
文章类型Article
语种英语
国家Peoples R China
英文摘要

Tumour radiotherapy resistance involves the cell cycle pathway. CDC25 phosphatases are key cell cycle regulators. However, how CDC25 activity is precisely controlled remains largely unknown. Here, we show that LIM domain-containing proteins, such as FHL1, increase inhibitory CDC25 phosphorylation by forming a complex with CHK2 and CDC25, and sequester CDC25 in the cytoplasm by forming another complex with 14-3-3 and CDC25, resulting in increased radioresistance in cancer cells. FHL1 expression, induced by ionizing irradiation in a SP1- and MLL1-dependent manner, positively correlates with radioresistance in cancer patients. We identify a cell-penetrating 11 amino-acid motif within LIM domains (eLIM) that is sufficient for binding CHK2 and CDC25, reducing the CHK2-CDC25 and CDC25-14-3-3 interaction and enhancing CDC25 activity and cancer radiosensitivity accompanied by mitotic catastrophe and apoptosis. Our results provide novel insight into molecular mechanisms underlying CDC25 activity regulation. LIM protein inhibition or use of eLIM may be new strategies for improving tumour radiosensitivity.


领域资源环境
收录类别SCI-E
WOS记录号WOS:000391940000001
WOS关键词DNA-DAMAGE RESPONSE ; ESTROGEN-RECEPTOR ; FHL1 EXPRESSION ; CDC25 ; BREAST ; 14-3-3-PROTEINS ; LOCALIZATION ; ACTIVATION ; SURVIVAL ; GENE
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
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文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/203766
专题资源环境科学
作者单位1.Beijing Inst Biotechnol, Dept Med Mol Biol, Collaborat Innovat Ctr Canc Med, Beijing 100850, Peoples R China;
2.Dalian Med Univ, Ctr Canc, Inst Canc Stem Cell, Liaoning 116023, Peoples R China;
3.Peoples Liberat Army Gen Hosp, Dept Oncol, Beijing 100853, Peoples R China;
4.Peoples Liberat Army Gen Hosp, Hainan Branch, Dept Thorac Surg, Hainan 572013, Peoples R China;
5.China Med Univ, Shengjing Hosp, Med Res Ctr, Liaoning 110004, Peoples R China;
6.Beijing Inst Biotechnol, Dept Microorganism Engn, Beijing 100071, Peoples R China;
7.Peoples Liberat Army Gen Hosp, Dept Gynecol & Obstet, Beijing 100853, Peoples R China;
8.Peoples Liberat Army Gen Hosp, Dept Endocrinol, Beijing 100853, Peoples R China;
9.Peoples Liberat Army Gen Hosp, Dept Thorac Surg, Beijing 100853, Peoples R China;
10.Peoples Liberat Army, Dept Oncol, Hosp 307, Beijing 100071, Peoples R China;
11.Peking Univ, Dept Renal Canc & Melanoma, Canc Hosp & Inst, Beijing 100142, Peoples R China;
12.Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Radiotherapy, Xian 710061, Peoples R China
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Xu, Xiaojie,Fan, Zhongyi,Liang, Chaoyang,et al. A signature motif in LIM proteins mediates binding to checkpoint proteins and increases tumour radiosensitivity[J]. NATURE COMMUNICATIONS,2017,8.
APA Xu, Xiaojie.,Fan, Zhongyi.,Liang, Chaoyang.,Li, Ling.,Wang, Lili.,...&Ye, Qinong.(2017).A signature motif in LIM proteins mediates binding to checkpoint proteins and increases tumour radiosensitivity.NATURE COMMUNICATIONS,8.
MLA Xu, Xiaojie,et al."A signature motif in LIM proteins mediates binding to checkpoint proteins and increases tumour radiosensitivity".NATURE COMMUNICATIONS 8(2017).
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