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Jung, Hee Jung
식물 노화·수명 연구단
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RUNX3 methylation drives hypoxia-induced cell proliferation and antiapoptosis in early tumorigenesis

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Title
RUNX3 methylation drives hypoxia-induced cell proliferation and antiapoptosis in early tumorigenesis
Author(s)
Sun Hee Lee; Do Young Hyeon; Soo-Hyun Yoon; Ji-Hak Jeong; Saeng-Myung Han; Ju-Won Jang; Minh Phuong Nguyen; Xin-Zi Chi; Sojin An; Kyung-gi Hyun; Hee-Jung Jung; Ji-Joon Song; Suk-Chul Bae; Woo-Ho Kim; Daehee Hwang; You Mie Lee
Publication Date
2021-04
Journal
CELL DEATH AND DIFFERENTIATION, v.28, pp.1251 - 1269
Publisher
NATURE PUBLISHING GROUP
Abstract
© 2020, The Author(s).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
URI
https://pr.ibs.re.kr/handle/8788114/9460
DOI
10.1038/s41418-020-00647-1
ISSN
1350-9047
Appears in Collections:
Center for Plant Aging Research (식물 노화·수명 연구단) > 1. Journal Papers (저널논문)
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