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O-GlcNAcylation of the Tumor Suppressor FOXO3 Triggers Aberrant Cancer Cell Growth

DC FieldValueLanguage
dc.contributor.author강창무-
dc.contributor.author김은경-
dc.contributor.author김호근-
dc.date.accessioned2018-08-28T17:17:28Z-
dc.date.available2018-08-28T17:17:28Z-
dc.date.issued2018-
dc.identifier.issn0008-5472-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/162452-
dc.description.abstractPosttranslational modifications of tumor suppressors can induce abnormal cell growth. Here, we identify site-specific O-GlcNAcylation as a critical block of FOXO3 that may abrogate a part of the p53 pathway, resulting in aberrant cancer cell growth. Of seven O-GlcNAcylation sites identified within the FOXO3 transactivation domain, we found that changes in O-GlcNAcylation at Ser284 modulated p21-mediated cancer cell growth. Overexpression of either O-GlcNAcylated FOXO3 (FOX-OV) or a Ser-to-Ala mutant (S284A) in PANC-1 cells indicated that S284 O-GlcNAc acts as a critical block of the FOXO tumor suppressor and induces proliferation in PANC-1 cancer cells by stimulating the MDM2-p53-p21 axis. Furthermore, S284A mutant cells lacking S284 O-GlcNAc and FOX-OV cells exhibited opposing MDM2-p53-p21 axis expression patterns at both the mRNA and protein levels. Thus, our study provides evidence to support a role for S284 O-GlcNAc as a critical block of FOXO3 to induce subsequent cancer cell growth via abrogation of the p53 regulatory circuit.Significance: These findings highlight a posttranslational mechanism for indirect abrogation of the p53 pathway, one that may occur with some frequency in human cancer cells. Cancer Res; 78(5); 1214-24. (c)2018 AACR.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherAmerican Association for Cancer Research-
dc.relation.isPartOfCancer Research-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleO-GlcNAcylation of the Tumor Suppressor FOXO3 Triggers Aberrant Cancer Cell Growth-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine-
dc.contributor.departmentDept. of Surgery-
dc.contributor.googleauthorHeon Shin-
dc.contributor.googleauthorHyun-Jeong Cha-
dc.contributor.googleauthorKeun Na-
dc.contributor.googleauthorMin Jung Lee-
dc.contributor.googleauthorJin-Young Cho-
dc.contributor.googleauthorChae-Yeon Kim-
dc.contributor.googleauthorEun Kyung Kim-
dc.contributor.googleauthorChang Moo Kang-
dc.contributor.googleauthorHoguen Kim-
dc.contributor.googleauthorYoung-Ki Paik-
dc.identifier.doi10.1158/0008-5472.can-17-3512-
dc.contributor.localIdA00088-
dc.contributor.localIdA05461-
dc.contributor.localIdA01183-
dc.relation.journalcodeJ00452-
dc.identifier.eissn1538-7445-
dc.identifier.pmid29301793-
dc.identifier.urlhttp://cancerres.aacrjournals.org/content/78/5/1214-
dc.contributor.alternativeNameKang, Chang Moo-
dc.contributor.alternativeNameKim, Eun Kyung-
dc.contributor.alternativeNameKim, Ho Keun-
dc.contributor.affiliatedAuthorKang, Chang Moo-
dc.contributor.affiliatedAuthorKim, Eun Kyung-
dc.contributor.affiliatedAuthorKim, Ho Keun-
dc.citation.volume78-
dc.citation.number5-
dc.citation.startPage1214-
dc.citation.endPage1224-
dc.identifier.bibliographicCitationCancer Research, Vol.78(5) : 1214-1224, 2018-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers

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