ArticleNature cell biology2018
The mTOR-S6K pathway links growth signalling to DNA damage response by targeting RNF168.
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Article in Nature cell biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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79citing papers in PubMed
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79 citing papers in PubMed, 137 citations in OpenAlex.
- Molecular insights and therapeutic implications for the tumor suppressor role of LKB1 in non-small cell lung cancer.Cancer letters · 2026Review
- The metabolic enzyme GYS1 condenses with NONO/p54Cell death and differentiation · 2025Article
- Targeting the crosstalk of metabolism reprogramming and replication stress: novel strategy to combat cancer.Medical oncology (Northwood, London, England) · 2025Review
- RNF168 dephosphorylation ameliorates cognitive decline in Aβ-based mouse models of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- Comparison of the accuracy of predictive models in early detection of clinically relevant posthepatectomy liver failure.BMC cancer · 2025Article
- Long-term SiNPs exposure induced genetic instability and malignant transformation via SQSTM1/p62-mediated autophagy dysfunction in lungs.Materials today. Bio · 2025Article
- ZNF451 collaborates with RNF8 to regulate RNF168 localization and amplify ubiquitination signaling to promote DNA damage repair and regulate radiosensitivity.Cell death and differentiation · 2025Article
- Loss of genome maintenance is linked to mTOR complex 1 signaling and accelerates podocyte damage.JCI insight · 2025Article
- The Role of S6K1 in Aging and Alzheimer's Disease: Mechanistic Insights and Therapeutic Potential.International journal of molecular sciences · 2025Review
- Mechanism of nucleosomal H2A K13/15 monoubiquitination and adjacent dual monoubiquitination by RNF168.Nature chemical biology · 2025Article
- PIN1-SUMO2/3 motif suppresses excessive RNF168 chromatin accumulation and ubiquitin signaling to promote IR resistance.Nature communications · 2025Article
- Intrinsic differences in mTOR activity mediates lineage-specific responses to cyclophosphamide in mouse and human granulosa cells.Journal of ovarian research · 2025Article
- Review
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- Introduction of AGPAT3 gene as a regulator of cisplatin resistance in A2780 ovarian endometrioid carcinoma cell line.PloS one · 2025Article
- Premature aging and metabolic diseases: the impact of telomere attrition.Frontiers in aging · 2025Review
- NUFIP1 integrates amino acid sensing and DNA damage response to maintain the intestinal homeostasis.Nature metabolism · 2025Article
- R-loop formation contributes to mTORC1 activation-dependent DNA replication stress induced by p53 deficiency.Acta biochimica et biophysica Sinica · 2024Article
- Targeting the HECTD3-p62 axis increases the radiosensitivity of triple negative breast cancer cells.Cell death discovery · 2024Article
- The PRC2.1 Subcomplex Opposes G1 Progression through Regulation of CCND1 and CCND2.bioRxiv : the preprint server for biology · 2024Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 9 institutions in 2 countries.
Xiaoduo XieState Key Laboratory of Cell Biology, CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Hongli HuState Key Laboratory of Cell Biology, CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Xinyuan TongState Key Laboratory of Cell Biology, CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Long LiState Key Laboratory of Cell Biology, CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Xiangyuan LiuState Key Laboratory of Cell Biology, CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Min ChenState Key Laboratory of Cell Biology, CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Huairui YuanThe Key Laboratory of Stem Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, University of Chinese Academy of Sciences, Shanghai, China.
Xia XieState Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Qingrun LiCAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0002-1644-0508
Yuxue ZhangState Key Laboratory of Cell Biology, CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Huafang OuyangState Key Laboratory of Cell Biology, CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Mengqi WeiNational Center for Protein Science Shanghai, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Jing HuangNational Center for Protein Science Shanghai, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Pengda LiuDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Wenjian GanDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Yong LiuDepartment of Radiation Oncology, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.
Anyong XieSir Run Run Shaw Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Xiaoling KuaiDepartment of Gastroenterology, Nantong University Affiliated Hospital, Nantong, Jiangsu, China.
Gung-Wei ChirnOrigiMed Co. Ltd, Shanghai, China.
Hu ZhouDepartment of Analytical Chemistry and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Rong ZengCAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Ronggui HuState Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Jun QinThe Key Laboratory of Stem Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, University of Chinese Academy of Sciences, Shanghai, China.
Fei-Long MengState Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
Wenyi WeiDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0512-3811
Hongbin JiState Key Laboratory of Cell Biology, CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.ORCID http://orcid.org/0000-0003-0891-6390
Daming GaoState Key Laboratory of Cell Biology, CAS Key Laboratory of Systems Biology, CAS Center for Excellence in Molecular Cell Science, Innovation Center for Cell Signaling Network, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. dgao@sibcb.ac.cn.ORCID http://orcid.org/0000-0003-4374-1055
Center for Excellence in Molecular Cell Science · CNBeth Israel Deaconess Medical Center · USShanghai Jiao Tong University · CNNantong University · CNShanghai First People's Hospital · CNShanghai Institute of Materia Medica · CNSir Run Run Shaw Hospital · CNUnimed Medical Institute · CNUniversity of North Carolina at Chapel Hill · US
Funding
Training Program in Angiogenesis &InflammationT32HL007893 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI DVORAK, HAROLD FISHER · 1998 to 2017
$5.5MElucidating a Novel Akt Activation Mechanism for Targeted Prostate Cancer TherapyR00CA181342 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LIU, PENGDA · 2016 to 2018
$653kElucidating a Novel Akt Activation Mechanism for Targeted Prostate Cancer TherapyK99CA181342 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI LIU, PENGDA · 2014 to 2015
$339kNCI NIH HHS K99 CA181342NCI NIH HHS R00 CA181342NHLBI NIH HHS T32 HL007893
Abstract
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.
Indexed as
Cell ProliferationDNA RepairA549 CellsAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsDNA Breaks, Double-StrandedFemaleHCT116 CellsHEK293 CellsHumansMaleMechanistic Target of Rapamycin Complex 1MiceMice, Inbred BALB CMice, NudeAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesMechanistic Target of Rapamycin Complex 1MTOR protein, humanmTOR protein, mouseProtein Serine-Threonine Kinasesribosomal protein S6 kinase, 70kD, polypeptide 1Ribosomal Protein S6 Kinases, 70-kDaRibosomal Protein S6 Kinases, 90-kDaRNF168 protein, humanRNF168 protein, mouseRps6ka1 protein, mouseSTK11 protein, humanStk11 protein, mouseTOR Serine-Threonine KinasesUbiquitin-Protein Ligases
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