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Renal Cell Carcinoma Is Abrogated by p53 Stabilization through Transglutaminase 2 Inhibition

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dc.contributor.author라선영-
dc.contributor.author권우선-
dc.date.accessioned2019-02-14T01:51:07Z-
dc.date.available2019-02-14T01:51:07Z-
dc.date.issued2018-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/167253-
dc.description.abstractIn general, expression of transglutaminase 2 (TGase 2) is upregulated in renal cell carcinoma (RCC), resulting in p53 instability. Previous studies show that TGase 2 binds to p53 and transports it to the autophagosome. Knockdown or inhibition of TGase 2 in RCC induces p53-mediated apoptosis. Here, we screened a chemical library for TGase 2 inhibitors and identified streptonigrin as a potential therapeutic compound for RCC. Surface plasmon resonance and mass spectroscopy were used to measure streptonigrin binding to TGase 2. Mass spectrometry analysis revealed that streptonigrin binds to the N-terminus of TGase 2 (amino acids 95⁻116), which is associated with inhibition of TGase 2 activity in vitro and with p53 stabilization in RCC. The anti-cancer effects of streptonigrin on RCC cell lines were demonstrated in cell proliferation and cell death assays. In addition, a single dose of streptonigrin (0.2 mg/kg) showed marked anti-tumor effects in a preclinical RCC model by stabilizing p53. Inhibition of TGase 2 using streptonigrin increased p53 stability, which resulted in p53-mediated apoptosis of RCC. Thus, targeting TGase 2 may be a new therapeutic approach to RCC.-
dc.description.statementOfResponsibilityopen-
dc.formatapplication/pdf-
dc.languageEnglish-
dc.publisherMDPI-
dc.relation.isPartOfCANCERS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rightshttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.titleRenal Cell Carcinoma Is Abrogated by p53 Stabilization through Transglutaminase 2 Inhibition-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학교실)-
dc.contributor.googleauthorSeon-Hyeong Lee-
dc.contributor.googleauthorWon-Kyu Lee-
dc.contributor.googleauthorNayeon Kim-
dc.contributor.googleauthorJoon Hee Kang-
dc.contributor.googleauthorKyung-Hee Kim-
dc.contributor.googleauthorSeul-Gi Kim-
dc.contributor.googleauthorJae-Seon Lee-
dc.contributor.googleauthorSoohyun Lee-
dc.contributor.googleauthorJongkook Lee-
dc.contributor.googleauthorJungnam Joo-
dc.contributor.googleauthorWoo Sun Kwon-
dc.contributor.googleauthorSun Young Rha-
dc.contributor.googleauthorSoo-Youl Kim-
dc.identifier.doi10.3390/cancers10110455-
dc.contributor.localIdA01316-
dc.relation.journalcodeJ03449-
dc.identifier.eissn2072-6694-
dc.identifier.pmid30463244-
dc.subject.keywordapoptosis-
dc.subject.keywordp53-
dc.subject.keywordrenal cell carcinoma-
dc.subject.keywordstreptonigrin-
dc.subject.keywordtransglutaminase 2-
dc.contributor.alternativeNameRha, Sun Young-
dc.contributor.affiliatedAuthor라선영-
dc.citation.volume10-
dc.citation.number11-
dc.citation.startPageE455-
dc.identifier.bibliographicCitationCANCERS, Vol.10(11) : E455, 2018-
dc.identifier.rimsid61458-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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