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dc.contributor.author Lee, Sun Hee -
dc.contributor.author Hyeon, Do Young -
dc.contributor.author Yoon, Soo-Hyun -
dc.contributor.author Jeong, Ji-Hak -
dc.contributor.author Han, Saeng-Myung -
dc.contributor.author Jang, Ju-Won -
dc.contributor.author Minh Phuong Nguyen -
dc.contributor.author Chi, Xin-Zi -
dc.contributor.author An, Sojin -
dc.contributor.author Hyun, Kyung-gi -
dc.contributor.author Jung, Hee-Jung -
dc.contributor.author Song, Ji-Joon -
dc.contributor.author Bae, Suk-Chul -
dc.contributor.author Kim, Woo-Ho -
dc.contributor.author Hwang, Daehee -
dc.contributor.author Lee, You Mie -
dc.date.accessioned 2021-01-22T07:33:34Z -
dc.date.available 2021-01-22T07:33:34Z -
dc.date.created 2020-11-13 -
dc.date.issued 2021-04 -
dc.identifier.issn 1350-9047 -
dc.identifier.uri http://hdl.handle.net/20.500.11750/12786 -
dc.description.abstract Inactivation of tumor suppressor Runt-related transcription factor 3 (RUNX3) plays an important role during early tumorigenesis. However, posttranslational modifications (PTM)-based mechanism for the inactivation of RUNX3 under hypoxia is still not fully understood. Here, we demonstrate a mechanism that G9a, lysine-specific methyltransferase (KMT), modulates RUNX3 through PTM under hypoxia. Hypoxia significantly increased G9a protein level and G9a interacted with RUNX3 Runt domain, which led to increased methylation of RUNX3 at K129 and K171. This methylation inactivated transactivation activity of RUNX3 by reducing interactions with CBFβ and p300 cofactors, as well as reducing acetylation of RUNX3 by p300, which is involved in nucleocytoplasmic transport by importin-α1. G9a-mediated methylation of RUNX3 under hypoxia promotes cancer cell proliferation by increasing cell cycle or cell division, while suppresses immune response and apoptosis, thereby promoting tumor growth during early tumorigenesis. Our results demonstrate the molecular mechanism of RUNX3 inactivation by G9a-mediated methylation for cell proliferation and antiapoptosis under hypoxia, which can be a therapeutic or preventive target to control tumor growth during early tumorigenesis. © 2020, The Author(s). -
dc.language English -
dc.publisher Springer Nature -
dc.title RUNX3 methylation drives hypoxia-induced cell proliferation and antiapoptosis in early tumorigenesis -
dc.type Article -
dc.identifier.doi 10.1038/s41418-020-00647-1 -
dc.identifier.wosid 000584874800001 -
dc.identifier.scopusid 2-s2.0-85094180700 -
dc.identifier.bibliographicCitation Cell Death and Differentiation, v.28, no.4, pp.1251 - 1269 -
dc.description.isOpenAccess TRUE -
dc.subject.keywordPlus GENE -
dc.subject.keywordPlus EXPRESSION -
dc.subject.keywordPlus BINDING -
dc.subject.keywordPlus GASTRIC-CANCER -
dc.subject.keywordPlus TUMOR-SUPPRESSOR -
dc.subject.keywordPlus PROTEIN -
dc.citation.endPage 1269 -
dc.citation.number 4 -
dc.citation.startPage 1251 -
dc.citation.title Cell Death and Differentiation -
dc.citation.volume 28 -
dc.description.journalRegisteredClass scie -
dc.description.journalRegisteredClass scopus -
dc.relation.journalResearchArea Biochemistry & Molecular Biology; Cell Biology -
dc.relation.journalWebOfScienceCategory Biochemistry & Molecular Biology; Cell Biology -
dc.type.docType Article -
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