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Article: S6K1 is a multifaceted regulator of Mdm2 that connects nutrient status and DNA damage response

TitleS6K1 is a multifaceted regulator of Mdm2 that connects nutrient status and DNA damage response
Authors
Issue Date2010
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/emboj/index.html
Citation
Embo Journal, 2010, v. 29 n. 17, p. 2994-3006 How to Cite?
Abstractp53 mediates DNA damage-induced cell-cycle arrest, apoptosis, or senescence, and it is controlled by Mdm2, which mainly ubiquitinates p53 in the nucleus and promotes p53 nuclear export and degradation. By searching for the kinases responsible for Mdm2 S163 phosphorylation under genotoxic stress, we identified S6K1 as a multifaceted regulator of Mdm2. DNA damage activates mTOR-S6K1 through p38α MAPK. The activated S6K1 forms a tighter complex with Mdm2, inhibits Mdm2-mediated p53 ubiquitination, and promotes p53 induction, in addition to phosphorylating Mdm2 on S163. Deactivation of mTOR-S6K1 signalling leads to Mdm2 nuclear translocation, which is facilitated by S163 phosphorylation, a reduction in p53 induction, and an alteration in p53-dependent cell death. These findings thus establish mTOR-S6K1 as a novel regulator of p53 in DNA damage response and likely in tumorigenesis. S6K1-Mdm2 interaction presents a route for cells to incorporate the metabolic/energy cues into DNA damage response and links the aging-controlling Mdm2-p53 and mTOR-S6K pathways. © 2010 European Molecular Biology Organization.
Persistent Identifierhttp://hdl.handle.net/10722/183399
ISSN
2015 Impact Factor: 9.643
2015 SCImago Journal Rankings: 7.450
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLai, KPen_US
dc.contributor.authorLeong, WFen_US
dc.contributor.authorChau, JFLen_US
dc.contributor.authorJia, Den_US
dc.contributor.authorZeng, Len_US
dc.contributor.authorLiu, Hen_US
dc.contributor.authorHe, Len_US
dc.contributor.authorHao, Aen_US
dc.contributor.authorZhang, Hen_US
dc.contributor.authorMeek, Den_US
dc.contributor.authorVelagapudi, Cen_US
dc.contributor.authorHabib, SLen_US
dc.contributor.authorLi, Ben_US
dc.date.accessioned2013-05-27T07:12:35Z-
dc.date.available2013-05-27T07:12:35Z-
dc.date.issued2010en_US
dc.identifier.citationEmbo Journal, 2010, v. 29 n. 17, p. 2994-3006en_US
dc.identifier.issn0261-4189en_US
dc.identifier.urihttp://hdl.handle.net/10722/183399-
dc.description.abstractp53 mediates DNA damage-induced cell-cycle arrest, apoptosis, or senescence, and it is controlled by Mdm2, which mainly ubiquitinates p53 in the nucleus and promotes p53 nuclear export and degradation. By searching for the kinases responsible for Mdm2 S163 phosphorylation under genotoxic stress, we identified S6K1 as a multifaceted regulator of Mdm2. DNA damage activates mTOR-S6K1 through p38α MAPK. The activated S6K1 forms a tighter complex with Mdm2, inhibits Mdm2-mediated p53 ubiquitination, and promotes p53 induction, in addition to phosphorylating Mdm2 on S163. Deactivation of mTOR-S6K1 signalling leads to Mdm2 nuclear translocation, which is facilitated by S163 phosphorylation, a reduction in p53 induction, and an alteration in p53-dependent cell death. These findings thus establish mTOR-S6K1 as a novel regulator of p53 in DNA damage response and likely in tumorigenesis. S6K1-Mdm2 interaction presents a route for cells to incorporate the metabolic/energy cues into DNA damage response and links the aging-controlling Mdm2-p53 and mTOR-S6K pathways. © 2010 European Molecular Biology Organization.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/emboj/index.htmlen_US
dc.relation.ispartofEMBO Journalen_US
dc.subject.meshCell Cycleen_US
dc.subject.meshCell Lineen_US
dc.subject.meshDna Damageen_US
dc.subject.meshDna Repairen_US
dc.subject.meshDimerizationen_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshHumansen_US
dc.subject.meshPhosphorylationen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshProto-Oncogene Proteins C-Mdm2 - Metabolismen_US
dc.subject.meshRibosomal Protein S6 Kinases, 70-Kda - Metabolismen_US
dc.subject.meshSerine - Metabolismen_US
dc.subject.meshStress, Physiologicalen_US
dc.subject.meshTumor Suppressor Protein P53 - Metabolismen_US
dc.titleS6K1 is a multifaceted regulator of Mdm2 that connects nutrient status and DNA damage responseen_US
dc.typeArticleen_US
dc.identifier.emailLai, KP: ballllai@hotmail.comen_US
dc.identifier.authorityLai, KP=rp01753en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1038/emboj.2010.166en_US
dc.identifier.pmid20657550-
dc.identifier.scopuseid_2-s2.0-77956392880en_US
dc.identifier.hkuros223775-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77956392880&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume29en_US
dc.identifier.issue17en_US
dc.identifier.spage2994en_US
dc.identifier.epage3006en_US
dc.identifier.isiWOS:000282928500013-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLai, KP=7402135707en_US
dc.identifier.scopusauthoridLeong, WF=36846157200en_US
dc.identifier.scopusauthoridChau, JFL=15828893500en_US
dc.identifier.scopusauthoridJia, D=24484433400en_US
dc.identifier.scopusauthoridZeng, L=7401904330en_US
dc.identifier.scopusauthoridLiu, H=36067405700en_US
dc.identifier.scopusauthoridHe, L=55158160500en_US
dc.identifier.scopusauthoridHao, A=7003499024en_US
dc.identifier.scopusauthoridZhang, H=36071577100en_US
dc.identifier.scopusauthoridMeek, D=7005686811en_US
dc.identifier.scopusauthoridVelagapudi, C=25947864100en_US
dc.identifier.scopusauthoridHabib, SL=14719505600en_US
dc.identifier.scopusauthoridLi, B=7410078924en_US

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