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Truncated Adenomatous Polyposis Coli Mutation Induces Asef-Activated Golgi Fragmentation

DC FieldValueLanguage
dc.contributor.author김상범-
dc.date.accessioned2019-03-15T02:26:58Z-
dc.date.available2019-03-15T02:26:58Z-
dc.date.issued2018-
dc.identifier.issn0270-7306-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/167487-
dc.description.abstractAdenomatous polyposis coli (APC) is a key molecule to maintain cellular homeostasis in colonic epithelium by regulating cell-cell adhesion, cell polarity, and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (Asef). The APC-activated Asef stimulates the small GTPase, which leads to decreased cell-cell adherence and cell polarity, and enhanced cell migration. In colorectal cancers, while truncated APC constitutively activates Asef and promotes cancer initiation and progression, regulation of Asef by full-length APC is still unclear. Here, we report the autoinhibition mechanism of full-length APC. We found that the armadillo repeats in full-length APC interact with the APC residues 1362 to 1540 (APC-2,3 repeats), and this interaction competes off and inhibits Asef. Deletion of APC-2,3 repeats permits Asef interactions leading to downstream signaling events, including the induction of Golgi fragmentation through the activation of the Asef-ROCK-MLC2. Truncated APC also disrupts protein trafficking and cholesterol homeostasis by inhibition of SREBP2 activity in a Golgi fragmentation-dependent manner. Our study thus uncovers the autoinhibition mechanism of full-length APC and a novel gain of function of truncated APC in regulating Golgi structure, as well as cholesterol homeostasis, which provides a potential target for pharmaceutical intervention against colon cancers.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherAmerican Society for Microbiology-
dc.relation.isPartOfMOLECULAR AND CELLULAR BIOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleTruncated Adenomatous Polyposis Coli Mutation Induces Asef-Activated Golgi Fragmentation-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentBioMedical Science Institute (의생명과학부)-
dc.contributor.googleauthorSang Bum Kim-
dc.contributor.googleauthorLu Zhang-
dc.contributor.googleauthorJimok Yoon-
dc.contributor.googleauthorJeon Lee-
dc.contributor.googleauthorJaewon Min-
dc.contributor.googleauthorWenlin Li-
dc.contributor.googleauthorNick V. Grishin-
dc.contributor.googleauthorYoung-Ah Moon-
dc.contributor.googleauthorWoodring E. Wright-
dc.contributor.googleauthorJerry W. Shay-
dc.identifier.doi10.1128/MCB.00135-18-
dc.contributor.localIdA05691-
dc.relation.journalcodeJ02243-
dc.identifier.eissn1098-5549-
dc.identifier.pmid29866653-
dc.subject.keywordAPC-
dc.subject.keywordAsef-
dc.subject.keywordGolgi fragmentation-
dc.subject.keywordadenomatous polyposis coli-
dc.subject.keywordarmadillo repeats-
dc.citation.volume38-
dc.citation.number17-
dc.citation.startPagee00135-18-
dc.identifier.bibliographicCitationMOLECULAR AND CELLULAR BIOLOGY, Vol.38(17) : e00135-18, 2018-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers

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