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Chemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interaction

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dc.contributor.authorKim, Dae Gyu-
dc.contributor.authorLee, Jin Young-
dc.contributor.authorKwon, Nam Hoon-
dc.contributor.authorFang, Pengfei-
dc.contributor.authorZhang, Qian-
dc.contributor.authorWang, Jing-
dc.contributor.authorYoung, Nicolas L-
dc.contributor.authorGuo, Min-
dc.contributor.authorCho, Hye Young-
dc.contributor.authorMushtaq, Ameeq Ul-
dc.contributor.authorJeon, Young Ho-
dc.contributor.authorChoi, Jin Woo-
dc.contributor.authorHan, Jung Min-
dc.contributor.authorKang, Ho Woong-
dc.contributor.authorJoo, Jae Eun-
dc.contributor.authorHur, Youn-
dc.contributor.authorKang, Wonyoung-
dc.contributor.authorYang, Heekyoung-
dc.contributor.authorNam, Do-Hyun-
dc.contributor.authorLee, Mi-Sook-
dc.contributor.authorLee, Jung Weon-
dc.contributor.authorKim, Eun-Sook-
dc.contributor.authorMoon, Aree-
dc.contributor.authorKim, Kibom-
dc.contributor.authorKim, Doyeun-
dc.contributor.authorKang, Eun Joo-
dc.contributor.authorMoon, Youngji-
dc.contributor.authorRhee, Kyung Hee-
dc.contributor.authorHan, Byung Woo-
dc.contributor.authorYang, Jee Sun-
dc.contributor.authorHan, Gyoonhee-
dc.contributor.authorYang, Won Suk-
dc.contributor.authorLee, Cheolju-
dc.contributor.authorWang, Ming-Wei-
dc.contributor.authorKim, Sunghoon-
dc.creator한병우-
dc.date.accessioned2014-04-01T02:16:58Z-
dc.date.available2014-04-01T02:16:58Z-
dc.date.issued2014-01-
dc.identifier.citationNature Chemical Biology Vol.10 No.1, pp. 29-34-
dc.identifier.issn1552-4450 (print)-
dc.identifier.issn1552-4469 (print)-
dc.identifier.urihttp://hdl.handle.net/10371/91277-
dc.description.abstractLysyl-tRNA synthetase (KRS), a protein synthesis enzyme in the cytosol, relocates to the plasma membrane after a laminin signal and stabilizes a 67-kDa laminin receptor (67LR) that is implicated in cancer metastasis; however, its potential as an antimetastatic therapeutic target has not been explored. We found that the small compound BC-K-YH16899, which binds KRS, impinged on the interaction of KRS with 67LR and suppressed metastasis in three different mouse models. The compound inhibited the KRS-67LR interaction in two ways. First, it directly blocked the association between KRS and 67LR. Second, it suppressed the dynamic movement of the N-terminal extension of KRS and reduced membrane localization of KRS. However, it did not affect the catalytic activity of KRS. Our results suggest that specific modulation of a cancer-related KRS-67LR interaction may offer a way to control metastasis while avoiding the toxicities associated with inhibition of the normal functions of KRS.en
dc.description.sponsorshipThis work was supported by the Global Frontier Project (grants NRF-M1AXA002-2010-0029785 (S.K.), NRF-M1AXA002-2010-0029765 (Y.H.J.), NRF-2012M3A6A4054271 (J.W.L.) and NRF- 2012-054237 (B.W.H.)), the World Class University (grant R31-2008-000-10086-0 (G.H.)), the Proteogenomic Research Program (2012M3A9B9036679 (C.L.)) and by the National Research Foundation funded by the Ministry of Education, Science and Technology of Korea (grant ROA-2012-0006262 (A.M.)). This study was also funded by the Ministry for Health and Welfare Affairs of Korea through the Korea Healthcare Technology Research and Development Project (A092255 (D.-H.N.)) and by a grant from Gyeonggi Research Development Program (S.K.). This work was supported in part by grants from the US National Institutes of Health (GM100136 (M.G.)); the US National Science Foundation Division of Materials Research through DMR-11-57490 (A.G. Marshall, Florida State University); by the state of Florida (M.G.) and by a Kimmel Scholar Award for Cancer Research (M.G.). We appreciate A.G. Marshall for supporting the HDX-MS program and facility, M.-S. Seok (Korea University) for the preparation of the nanodisc and S.W. Lee (Sungkyunkwan University) for X-ray analysis.-
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.subject복합학en
dc.titleChemical inhibition of prometastatic lysyl-tRNA synthetase-laminin receptor interactionen
dc.typeArticle-
dc.author.alternative김대규-
dc.author.alternative이진영-
dc.author.alternative권남훈-
dc.author.alternative조혜영-
dc.author.alternative전영호-
dc.author.alternative최진우-
dc.author.alternative한정민-
dc.author.alternative강호웅-
dc.author.alternative주재은-
dc.author.alternative허 연-
dc.author.alternative강원영-
dc.author.alternative양희경-
dc.author.alternative남도현-
dc.author.alternative이미숙-
dc.author.alternative이정원-
dc.author.alternative김은숙-
dc.author.alternative문아리-
dc.author.alternative김기범-
dc.author.alternative김도연-
dc.author.alternative강은주-
dc.author.alternative문영지-
dc.author.alternative이경희-
dc.author.alternative한병우-
dc.author.alternative양지선-
dc.author.alternative한권희-
dc.author.alternative양원석-
dc.author.alternative이철주-
dc.author.alternative김성훈-
dc.identifier.doi10.1038/nchembio.1381-
dc.citation.journaltitleNature Chemical Biology-
dc.description.srndOAIID:oai:osos.snu.ac.kr:snu2014-01/102/0000012460/1-
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dc.description.srndPERF_CD:SNU2014-01-
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dc.description.srndEMP_ID:A078106-
dc.description.srndDEPT_CD:375-
dc.description.srndCITE_RATE:12.948-
dc.description.srndFILENAME:첨부된 내역이 없습니다.-
dc.description.srndDEPT_NM:약학과-
dc.description.srndEMAIL:bwhan@snu.ac.kr-
dc.description.srndSCOPUS_YN:Y-
dc.description.srndCONFIRM:Y-
dc.identifier.srnd2014-01/102/0000012460/1-
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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