Cited 31 times in
O-GlcNAcylation of the Tumor Suppressor FOXO3 Triggers Aberrant Cancer Cell Growth
DC Field | Value | Language |
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dc.contributor.author | 강창무 | - |
dc.contributor.author | 김호근 | - |
dc.contributor.author | 김은경 | - |
dc.date.accessioned | 2018-08-28T17:17:28Z | - |
dc.date.available | 2018-08-28T17:17:28Z | - |
dc.date.issued | 2018 | - |
dc.identifier.issn | 0008-5472 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/162452 | - |
dc.description.abstract | Posttranslational 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.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | American Association for Cancer Research | - |
dc.relation.isPartOf | CANCER RESEARCH | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.title | O-GlcNAcylation of the Tumor Suppressor FOXO3 Triggers Aberrant Cancer Cell Growth | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine | - |
dc.contributor.department | Dept. of Surgery | - |
dc.contributor.googleauthor | Heon Shin | - |
dc.contributor.googleauthor | Hyun-Jeong Cha | - |
dc.contributor.googleauthor | Keun Na | - |
dc.contributor.googleauthor | Min Jung Lee | - |
dc.contributor.googleauthor | Jin-Young Cho | - |
dc.contributor.googleauthor | Chae-Yeon Kim | - |
dc.contributor.googleauthor | Eun Kyung Kim | - |
dc.contributor.googleauthor | Chang Moo Kang | - |
dc.contributor.googleauthor | Hoguen Kim | - |
dc.contributor.googleauthor | Young-Ki Paik | - |
dc.identifier.doi | 10.1158/0008-5472.can-17-3512 | - |
dc.contributor.localId | A00088 | - |
dc.contributor.localId | A05461 | - |
dc.contributor.localId | A01183 | - |
dc.relation.journalcode | J00452 | - |
dc.identifier.eissn | 1538-7445 | - |
dc.identifier.pmid | 29301793 | - |
dc.identifier.url | http://cancerres.aacrjournals.org/content/78/5/1214 | - |
dc.contributor.alternativeName | Kang, Chang Moo | - |
dc.contributor.alternativeName | Kim, Ho Keun | - |
dc.contributor.affiliatedAuthor | Kang, Chang Moo | - |
dc.contributor.affiliatedAuthor | Kim, Ho Keun | - |
dc.citation.volume | 78 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 1214 | - |
dc.citation.endPage | 1224 | - |
dc.identifier.bibliographicCitation | CANCER RESEARCH, Vol.78(5) : 1214-1224, 2018 | - |
dc.identifier.rimsid | 60034 | - |
dc.type.rims | ART | - |
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