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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, Xiaoduo1; Hu, Hongli1; Tong, Xinyuan1; Li, Long1; Liu, Xiangyuan1; Chen, Min1; Zhang, Yuxue1; Ouyang, Huafang1; Ji, Hongbin1; Gao, Daming1
刊名NATURE CELL BIOLOGY
出版日期2018
卷号20期号:3页码:320-+
关键词pre-eclampsia complement 5a C5a receptor placenta trophoblasts angiogenesis arterial stiffness
ISSN号1465-7392
DOI10.1038/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.
学科主题Cell Biology
WOS关键词DOUBLE-STRAND BREAKS ; CALORIC RESTRICTION ; MAMMALIAN-CELLS ; IN-VITRO ; CANCER ; LKB1 ; PHOSPHORYLATION ; REPAIR ; UBIQUITIN ; METABOLISM
语种英语
WOS记录号WOS:000426059400014
出版者NATURE PUBLISHING GROUP
版本出版稿
源URL[http://202.127.25.144/handle/331004/729]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, CAS Ctr Excellence Mol Cell Sci,Univ Chinese Acad, State Key Lab Cell Biol,CAS Key Lab Syst Biol,Inn, Shanghai, Peoples R China;
2.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biol Sci,Shanghai Jiao Tong Univ,Sc, Key Lab Stem Cell Biol,Inst Hlth Sci,Univ Chinese, Shanghai, Peoples R China;
3.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, State Key Lab Mol Biol,Univ Chinese Acad Sci, Shanghai, Peoples R China;
4.Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol, CAS Key Lab Syst Biol,Univ Chinese Acad Sci, Shanghai, Peoples R China;
5.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Natl Ctr Prot Sci Shanghai, Univ Chinese Acad Sci, Shanghai, Peoples R China;
6.Chinese Acad Sci, Shanghai Sci Res Ctr, Shanghai, Peoples R China;
7.Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA;
8.Shanghai Jiao Tong Univ, Dept Radiat Oncol, Shanghai Gen Hosp, Shanghai, Peoples R China;
9.Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Hangzhou, Zhejiang, Peoples R China;
10.Zhejiang Univ, Sch Med, Inst Translat Med, Hangzhou, Zhejiang, 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.,...&,.(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：上海营养与健康研究所

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