The mTOR-S6K pathway links growth signalling to DNA damage response by targeting RNF168
文献类型：期刊论文
| 作者 | Xie, Xiaoduo15; Hu, Hongli15; Tong, Xinyuan15; Li, Long15; Liu, Xiangyuan15; Chen, Min15; Yuan, Huairui14; Xie, Xia13; Li, Qingrun12; Zhang, Yuxue15 |
| 刊名 | NATURE CELL BIOLOGY
 |
| 出版日期 | 2018-03 |
| 卷号 | 20期号:3页码:320-+ |
| ISSN号 | 1465-7392 |
| DOI | 10.1038/s41556-017-0033-8 |
| 文献子类 | Article |
| 英文摘要 | Growth signals, such as extracellular nutrients and growth factors, have substantial effects on genome integrity; however, the direct underlying link remains unclear. Here, we show that the mechanistic target of rapamycin (mTOR)-ribosomal S6 kinase (S6K) pathway, a central regulator of growth signalling, phosphorylates RNF168 at Ser60 to inhibit its E3 ligase activity, accelerate its proteolysis and impair its function in the DNA damage response, leading to accumulated unrepaired DNA and genome instability. Moreover, loss of the tumour suppressor liver kinase B1 (LKB1; also known as STK11) hyperactivates mTOR complex 1 (mTORC1)-S6K signalling and decreases RNF168 expression, resulting in defects in the DNA damage response. Expression of a phospho-deficient RNF168-S60A mutant rescues the DNA damage repair defects and suppresses tumorigenesis caused by Lkb1 loss. These results reveal an important function of mTORC1-S6K signalling in the DNA damage response and suggest a general mechanism that connects cell growth signalling to genome stability control. |
| WOS关键词 | DOUBLE-STRAND BREAKS ; CALORIC RESTRICTION ; MAMMALIAN-CELLS ; IN-VITRO ; CANCER ; LKB1 ; PHOSPHORYLATION ; REPAIR ; UBIQUITIN ; METABOLISM |
| 资助项目 | National Key Basic Research Program of China[2015CB964502] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19000000] ; National Science foundation of China[81372602] ; National Science foundation of China[81422033] ; National Science foundation of China[31401214] ; National Institutes of Health (USA)[1K99CA181342] ; National Institutes of Health (USA)[5T32HL007893] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000426059400014 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279879]  |
| 专题 | 分析化学研究室 |
| 通讯作者 | Gao, Daming |
| 作者单位 | 1.Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Hangzhou, Zhejiang, Peoples R China; 2.Univ North Carolina Chapel Hill, Dept Biochem & Biophys, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA 3.Chinese Acad Sci, Univ Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai, Peoples R China; 4.Chinese Acad Sci, Univ Chinese Acad Sci, Dept Analyt Chem, Shanghai, Peoples R China; 5.OrigiMed Co Ltd, Shanghai, Peoples R China; 6.Nantong Univ, Dept Gastroenterol, Affiliated Hosp, Nantong, Jiangsu, Peoples R China; 7.Zhejiang Univ, Sch Med, Inst Translat Med, Hangzhou, Zhejiang, Peoples R China; 8.Shanghai Jiao Tong Univ, Dept Radiat Oncol, Shanghai Gen Hosp, Shanghai, Peoples R China; 9.Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA; 10.Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Xie, Xiaoduo,Hu, Hongli,Tong, Xinyuan,et al. The mTOR-S6K pathway links growth signalling to DNA damage response by targeting RNF168[J]. NATURE CELL BIOLOGY,2018,20(3):320-+. |
| APA | Xie, Xiaoduo.,Hu, Hongli.,Tong, Xinyuan.,Li, Long.,Liu, Xiangyuan.,...&Gao, Daming.(2018).The mTOR-S6K pathway links growth signalling to DNA damage response by targeting RNF168.NATURE CELL BIOLOGY,20(3),320-+. |
| MLA | Xie, Xiaoduo,et al."The mTOR-S6K pathway links growth signalling to DNA damage response by targeting RNF168".NATURE CELL BIOLOGY 20.3(2018):320-+. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。