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High levels of Daxx due to low cellular levels of HSP25 in murine cancer cells result in inefficient adenovirus replication

DC Field Value Language
dc.contributor.author송재진-
dc.contributor.author최혜진-
dc.date.accessioned2019-12-18T00:37:36Z-
dc.date.available2019-12-18T00:37:36Z-
dc.date.issued2019-
dc.identifier.issn1226-3613-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/173147-
dc.description.abstractWhen the adenoviral protein E1B55K binds death domain-associated protein (Daxx), the proteasome-dependent degradation of Daxx is initiated, and adenoviral replication is effectively maintained. Here, we show that the cellular levels of Daxx differ between human and mouse cancer cell lines. Specifically, we observed higher cellular Daxx levels and the diminished replication of oncolytic adenovirus in mouse cancer cell lines, suggesting that cellular Daxx levels limit the replication of oncolytic adenoviruses that lack E1B55K in murine cells. Indeed, the replication of oncolytic adenoviruses that lack E1B55K was significantly increased following infection with oncolytic adenovirus expressing Daxx-specific shRNA. Cellular Daxx levels were decreased in mouse cells expressing heat shock protein 25 (HSP25; homolog of human HSP27) following heat shock or stable transfection with HSP25-bearing plasmids. Furthermore, Daxx expression in murine cell lines was primarily regulated at the transcriptional level via HSP25-mediated inhibition of the nuclear translocation of the signal transducer and activator of transcription 3 (stat3) protein, which typically upregulates Daxx transcription. Conversely, human HSP27 enhanced stat3 activity to increase Daxx transcription. Interestingly, human Daxx, but not mouse Daxx, was degraded as normal by ubiquitin-dependent lysosomal degradation; however, HSP27 downregulation induced the ubiquitin-independent proteasomal degradation of Daxx.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherNature Publishing Group-
dc.relation.isPartOfEXPERIMENTAL AND MOLECULAR MEDICINE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleHigh levels of Daxx due to low cellular levels of HSP25 in murine cancer cells result in inefficient adenovirus replication-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentBioMedical Science Institute (의생명과학부)-
dc.contributor.googleauthorZhezhu Han-
dc.contributor.googleauthorYeonsoo Joo-
dc.contributor.googleauthorJihyun Lee-
dc.contributor.googleauthorSuwan Ko-
dc.contributor.googleauthorRong Xu-
dc.contributor.googleauthorGeun-Hyeok Oh-
dc.contributor.googleauthorSoojin Choi-
dc.contributor.googleauthorJeong A. Hong-
dc.contributor.googleauthorHye Jin Choi-
dc.contributor.googleauthorJae J. Song-
dc.identifier.doi10.1038/s12276-019-0321-4-
dc.contributor.localIdA02056-
dc.contributor.localIdA04219-
dc.relation.journalcodeJ00860-
dc.identifier.eissn2092-6413-
dc.identifier.pmid31615977-
dc.contributor.alternativeNameSong, Jae Jin-
dc.contributor.affiliatedAuthor송재진-
dc.contributor.affiliatedAuthor최혜진-
dc.citation.volume51-
dc.citation.number10-
dc.citation.startPage122-
dc.identifier.bibliographicCitationEXPERIMENTAL AND MOLECULAR MEDICINE, Vol.51(10) : 122, 2019-
dc.identifier.rimsid63693-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers

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