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学科主题基础医学
The ribosomal protein S26 regulates p53 activity in response to DNA damage
Cui, D.1,2; Li, L.1,2; Lou, H.1,3; Sun, H.1,2; Ngai, S-M4,5; Shao, G.6; Tang, J.1,2
关键词ribosomal proteins RPS26 p53 DNA damage response p53 acetylation
刊名ONCOGENE
2014-04-24
DOI10.1038/onc.2013.170
33期:17页:2225-2235
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
研究领域[WOS]Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
关键词[WOS]DIAMOND-BLACKFAN ANEMIA ; MESSENGER-RNA ; INDUCED PHOSPHORYLATION ; MEDIATES STABILIZATION ; ACTIVATES P53 ; MDM2 ; L11 ; INHIBITION ; L5 ; PATHWAY
英文摘要

Ribosomal proteins have emerged as novel regulators of the Mdm2-p53 feedback loop, especially in the context of ribosomal stress. RPS26 is a recently identified Diamond-Blackfan Anemia-related ribosomal protein and its role in p53 activation has not been previously explored. In this study we found knockdown of RPS26 induced p53 stabilization and activation via a RPL11-dependent mechanism, resulting in p53-dependent cell growth inhibition. Moreover, RPS26 has the ability to interact with Mdm2 and inhibits Mdm2-mediated p53 ubiquitination that leads to p53 stabilization upon overexpression. Importantly, we discovered that RPS26 knockdown impaired p53′ s ability to transcriptionally activate its target genes in response to DNA damage, without affecting its stability. Accordingly, the cells lost the ability to induce G2/M cell cycle arrest. We further found that upon RPS26 knockdown, the DNA damage induced recruitment of p53 to the promoters of its target genes and p53 acetylation were both greatly reduced. In addition, RPS26 can interact with p53 independent of Mdm2 and coexist in a complex with p53 and p300. These data establish a role of RPS26 in DNA damage response by directly influencing p53 transcriptional activity, and suggest that RPS26 acts distinctively in different scenarios of p53 activation. Our finding also implicates p53 transcriptional activity control as an important mechanism of p53 regulation by ribosomal proteins.

语种英语
WOS记录号WOS:000334996000008
项目编号31171331 ; NCET-09-0737 ; 2010SKLAB06-5
资助机构National Natural Science Foundation of China ; Program for New Century Excellent Talents in University of China ; State Key Laboratory of Agrobiotechnology of China
引用统计
被引频次:36[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61680
专题北京大学基础医学院_细胞生物学系
作者单位1.China Agr Univ, State Key Lab Agrobiotechnol, Beijing 100193, Peoples R China
2.China Agr Univ, Coll Vet Med, Dept Basic Vet Med, Beijing 100193, Peoples R China
3.China Agr Univ, Coll Biol Sci, Beijing 100193, Peoples R China
4.Chinese Univ Hong Kong, Dept Biol, Hong Kong, Hong Kong, Peoples R China
5.Chinese Univ Hong Kong, State China Key Lab Agrobiotechnol, Hong Kong, Hong Kong, Peoples R China
6.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Cell Biol, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Cui, D.,Li, L.,Lou, H.,et al. The ribosomal protein S26 regulates p53 activity in response to DNA damage[J]. ONCOGENE,2014,33(17):2225-2235.
APA Cui, D..,Li, L..,Lou, H..,Sun, H..,Ngai, S-M.,...&Tang, J..(2014).The ribosomal protein S26 regulates p53 activity in response to DNA damage.ONCOGENE,33(17),2225-2235.
MLA Cui, D.,et al."The ribosomal protein S26 regulates p53 activity in response to DNA damage".ONCOGENE 33.17(2014):2225-2235.
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