Negative Regulation-Resistant p53 Variant Enhances Oncolytic Adenoviral Gene Therapy
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Koo, Taeyoung | - |
dc.contributor.author | Choi, Il-Kyu | - |
dc.contributor.author | Kim, Minjung | - |
dc.contributor.author | Lee, Jung-Sun | - |
dc.contributor.author | Oh, Eonju | - |
dc.contributor.author | Kim, Jungho | - |
dc.contributor.author | Yun, Chae-Ok | - |
dc.date.accessioned | 2021-08-02T19:28:48Z | - |
dc.date.available | 2021-08-02T19:28:48Z | - |
dc.date.created | 2021-05-12 | - |
dc.date.issued | 2012-06 | - |
dc.identifier.issn | 1043-0342 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/27527 | - |
dc.description.abstract | Intact p53 function is essential for responsiveness to cancer therapy. However, p53 activity is attenuated by the proto-oncoprotein Mdm2, the adenovirus protein E1B 55kD, and the p53 C-terminal domain. To confer resistance to Mdm2, E1B 55kD, and C-terminal negative regulation, we generated a p53 variant (p53VP Delta 30) by deleting the N-terminal and C-terminal regions of wild-type p53 and inserting the transcriptional activation domain of herpes simplex virus VP16 protein. The oncolytic adenovirus vector Ad-m Delta 19 expressing p53VP Delta 30 (Ad-m Delta 19/p53VP Delta 30) showed greater cytotoxicity than Ad-m Delta 19 expressing wild-type p53 or other p53 variants in human cancer cell lines. We found that Ad-m Delta 19/p53VP Delta 30 induced apoptosis through accumulation of p53VP Delta 30, regardless of endogenous p53 and Mdm2 status. Moreover, Ad-m Delta 19/p53VP Delta 30 showed a greater antitumor effect and increased survival rates of mice with U343 brain cancer xenografts that expressed wild-type p53 and high Mdm2 levels. To our knowledge, this is the first study reporting a p53 variant modified at the N terminus and C terminus that shows resistance to degradation by Mdm2 and E1B 55kD, as well as negative regulation by the p53 C terminus, without decreased trans-activation activity. Taken together, these results indicate that Ad-m Delta 19/p53VP Delta 30 shows potential for improving p53-mediated cancer gene therapy. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | MARY ANN LIEBERT INC | - |
dc.title | Negative Regulation-Resistant p53 Variant Enhances Oncolytic Adenoviral Gene Therapy | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Yun, Chae-Ok | - |
dc.identifier.doi | 10.1089/hum.2011.114 | - |
dc.identifier.scopusid | 2-s2.0-84864365426 | - |
dc.identifier.wosid | 000306356700009 | - |
dc.identifier.bibliographicCitation | HUMAN GENE THERAPY, v.23, no.6, pp.609 - 622 | - |
dc.relation.isPartOf | HUMAN GENE THERAPY | - |
dc.citation.title | HUMAN GENE THERAPY | - |
dc.citation.volume | 23 | - |
dc.citation.number | 6 | - |
dc.citation.startPage | 609 | - |
dc.citation.endPage | 622 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biotechnology & Applied Microbiology | - |
dc.relation.journalResearchArea | Genetics & Heredity | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Biotechnology & Applied Microbiology | - |
dc.relation.journalWebOfScienceCategory | Genetics & Heredity | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | TUMOR-SUPPRESSOR P53 | - |
dc.subject.keywordPlus | CANCER-THERAPY | - |
dc.subject.keywordPlus | DNA-BINDING | - |
dc.subject.keywordPlus | APOPTOSIS | - |
dc.subject.keywordPlus | MDM2 | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | CELLS | - |
dc.subject.keywordPlus | AMPLIFICATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | DATABASE | - |
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.
222, Wangsimni-ro, Seongdong-gu, Seoul, 04763, Korea+82-2-2220-1365
COPYRIGHT © 2021 HANYANG UNIVERSITY.
Certain data included herein are derived from the © Web of Science of Clarivate Analytics. All rights reserved.
You may not copy or re-distribute this material in whole or in part without the prior written consent of Clarivate Analytics.