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Small-molecule binding of the axin RGS domain promotes β-catenin and Ras degradation.

DC Field Value Language
dc.contributor.author김호근-
dc.date.accessioned2017-02-27T08:33:53Z-
dc.date.available2017-02-27T08:33:53Z-
dc.date.issued2016-
dc.identifier.issn1552-4450-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/147223-
dc.description.abstractBoth the Wnt/β-catenin and Ras pathways are aberrantly activated in most human colorectal cancers (CRCs) and interact cooperatively in tumor promotion. Inhibition of these signaling may therefore be an ideal strategy for treating CRC. We identified KY1220, a compound that destabilizes both β-catenin and Ras, via targeting the Wnt/β-catenin pathway, and synthesized its derivative KYA1797K. KYA1797K bound directly to the regulators of G-protein signaling domain of axin, initiating β-catenin and Ras degradation through enhancement of the β-catenin destruction complex activating GSK3β. KYA1797K effectively suppressed the growth of CRCs harboring APC and KRAS mutations, as shown by various in vitro studies and by in vivo studies using xenograft and transgenic mouse models of tumors induced by APC and KRAS mutations. Destabilization of both β-catenin and Ras via targeting axin is a potential therapeutic strategy for treatment of CRC and other type cancers activated Wnt/β-catenin and Ras pathways.-
dc.description.statementOfResponsibilityrestriction-
dc.format.extent593~600-
dc.languageEnglish-
dc.publisherNature Pub. Group-
dc.relation.isPartOfNATURE CHEMICAL BIOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAnimals-
dc.subject.MESHAxin Protein/chemistry*-
dc.subject.MESHAxin Protein/metabolism*-
dc.subject.MESHBinding Sites-
dc.subject.MESHCell Proliferation/drug effects-
dc.subject.MESHColorectal Neoplasms/drug therapy-
dc.subject.MESHColorectal Neoplasms/genetics-
dc.subject.MESHColorectal Neoplasms/pathology-
dc.subject.MESHGenes, APC-
dc.subject.MESHGenes, ras-
dc.subject.MESHHumans-
dc.subject.MESHMice-
dc.subject.MESHMice, Transgenic-
dc.subject.MESHNeoplasms, Experimental/drug therapy-
dc.subject.MESHNeoplasms, Experimental/genetics-
dc.subject.MESHNeoplasms, Experimental/pathology-
dc.subject.MESHProtein Stability/drug effects-
dc.subject.MESHProto-Oncogene Proteins p21(ras)/genetics-
dc.subject.MESHProto-Oncogene Proteins p21(ras)/metabolism*-
dc.subject.MESHRGS Proteins/chemistry*-
dc.subject.MESHRGS Proteins/metabolism-
dc.subject.MESHSmall Molecule Libraries/chemistry*-
dc.subject.MESHSmall Molecule Libraries/pharmacology*-
dc.subject.MESHThiohydantoins/chemical synthesis-
dc.subject.MESHThiohydantoins/chemistry-
dc.subject.MESHThiohydantoins/pharmacology*-
dc.subject.MESHWnt Signaling Pathway/drug effects-
dc.subject.MESHbeta Catenin/chemistry-
dc.subject.MESHbeta Catenin/metabolism*-
dc.titleSmall-molecule binding of the axin RGS domain promotes β-catenin and Ras degradation.-
dc.typeArticle-
dc.publisher.locationUnited States-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Pathology-
dc.contributor.googleauthorPu-Hyeon Cha-
dc.contributor.googleauthorYong-Hee Cho-
dc.contributor.googleauthorSang-Kyu Lee-
dc.contributor.googleauthorJaeHeon Lee-
dc.contributor.googleauthorWoo-Jeong Jeong-
dc.contributor.googleauthorByoung-San Moon-
dc.contributor.googleauthorJi-Hye Yun-
dc.contributor.googleauthorJee Sun Yang-
dc.contributor.googleauthorSooho Choi-
dc.contributor.googleauthorJuyong Yoon-
dc.contributor.googleauthorHyun-Yi Kim-
dc.contributor.googleauthorMi-Yeon Kim-
dc.contributor.googleauthorSaluja Kaduwal-
dc.contributor.googleauthorWeontae Lee-
dc.contributor.googleauthorDo Sik Min-
dc.contributor.googleauthorHoguen Kim-
dc.contributor.googleauthorGyoonhee Han-
dc.contributor.googleauthorKang-Yell Choi-
dc.identifier.doi10.1038/nchembio.2103-
dc.contributor.localIdA01183-
dc.relation.journalcodeJ02292-
dc.identifier.eissn1552-4469-
dc.identifier.pmid27294323-
dc.identifier.urlhttp://www.nature.com/nchembio/journal/v12/n8/full/nchembio.2103.html-
dc.contributor.alternativeNameKim, Ho Keun-
dc.contributor.affiliatedAuthorKim, Ho Keun-
dc.citation.volume12-
dc.citation.number8-
dc.citation.startPage593-
dc.citation.endPage600-
dc.identifier.bibliographicCitationNATURE CHEMICAL BIOLOGY, Vol.12(8) : 593-600, 2016-
dc.date.modified2017-02-24-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers

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