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Mechanism mediated by a noncoding RNA, nc886, in the cytotoxicity of a DNA-reactive compound

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dc.contributor.author김형표-
dc.contributor.author송민지-
dc.date.accessioned2020-02-26T06:36:19Z-
dc.date.available2020-02-26T06:36:19Z-
dc.date.issued2019-
dc.identifier.issn0027-8424-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/175217-
dc.description.abstractDNA-reactive compounds are harnessed for cancer chemotherapy. Their genotoxic effects are considered to be the main mechanism for the cytotoxicity to date. Because this mechanism preferentially affects actively proliferating cells, it is postulated that the cytotoxicity is specific to cancer cells. Nonetheless, they do harm normal quiescent cells, suggesting that there are other cytotoxic mechanisms to be uncovered. By employing doxorubicin as a representative DNA-reactive compound, we have discovered a cytotoxic mechanism that involves a cellular noncoding RNA (ncRNA) nc886 and protein kinase R (PKR) that is a proapoptotic protein. nc886 is transcribed by RNA polymerase III (Pol III), binds to PKR, and prevents it from aberrant activation in most normal cells. We have shown here that doxorubicin evicts Pol III from DNA and, thereby, shuts down nc886 transcription. Consequently, the instantaneous depletion of nc886 provokes PKR and leads to apoptosis. In a short-pulse treatment of doxorubicin, these events are the main cause of cytotoxicity preceding the DNA damage response in a 3D culture system as well as the monolayer cultures. By identifying nc886 as a molecular signal for PKR to sense doxorubicin, we have provided an explanation for the conundrum why DNA-damaging drugs can be cytotoxic to quiescent cells that have the competent nc886/PKR pathway.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherNational Academy of Sciences-
dc.relation.isPartOfPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.titleMechanism mediated by a noncoding RNA, nc886, in the cytotoxicity of a DNA-reactive compound-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Tropica Medicine (열대의학교실)-
dc.contributor.googleauthorNawapol Kunkeaw-
dc.contributor.googleauthorYeon-Su Lee-
dc.contributor.googleauthorWonkyun Ronny Im-
dc.contributor.googleauthorJiyoung Joan Jang-
dc.contributor.googleauthorMin-Ji Song-
dc.contributor.googleauthorBobae Yang-
dc.contributor.googleauthorJong-Lyul Park-
dc.contributor.googleauthorSeon-Young Kim-
dc.contributor.googleauthorYongsuk Ku-
dc.contributor.googleauthorYoosik Kim-
dc.contributor.googleauthorSangmin Kang-
dc.contributor.googleauthorHye-ram Jo-
dc.contributor.googleauthorJae-Hoon Jeong-
dc.contributor.googleauthorHyun-Sung Lee-
dc.contributor.googleauthorJu-Seog Lee-
dc.contributor.googleauthorHyoung-Pyo Kim-
dc.contributor.googleauthorBetty H. Johnson-
dc.contributor.googleauthorIn-Hoo Kim-
dc.contributor.googleauthorYong Sun Lee-
dc.identifier.doi10.1073/pnas.1814510116-
dc.contributor.localIdA01163-
dc.contributor.localIdA02025-
dc.relation.journalcodeJ02550-
dc.identifier.eissn1091-6490-
dc.identifier.pmid30948645-
dc.subject.keywordRNA polymerase III-
dc.subject.keywordcytotoxicity-
dc.subject.keyworddoxorubicin-
dc.subject.keywordnc886-
dc.subject.keywordprotein kinase R-
dc.contributor.alternativeNameKim, Hyoung Pyo-
dc.contributor.affiliatedAuthor김형표-
dc.contributor.affiliatedAuthor송민지-
dc.citation.volume116-
dc.citation.number17-
dc.citation.startPage8289-
dc.citation.endPage8294-
dc.identifier.bibliographicCitationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol.116(17) : 8289-8294, 2019-
dc.identifier.rimsid64210-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Tropica Medicine (열대의학교실) > 1. Journal Papers

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