한빛사논문
- 조회1,130
Sun Hee Lee1, Do Young Hyeon2, Soo-Hyun Yoon1, Ji-Hak Jeong1, Saeng-Myung Han1,3, Ju-Won Jang4, Minh Phuong Nguyen1,3,8, Xin-Zi Chi4, Sojin An5, Kyung-gi Hyun5, Hee-Jung Jung6, Ji-Joon Song5, Suk-Chul Bae4, Woo-Ho Kim7, Daehee Hwang2,6,*, You Mie Lee1,*
1Vessel-Organ Interaction Research Center, VOICE (MRC), Department of Molecular Pathophysiology, College of Pharmacy, Kyungpook National University, Daegu 41566, Republic of Korea
2School of Biological Sciences, Seoul National University, Seoul 08826, Republic of Korea
3School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 41566, Republic of Korea
4Department of Biochemistry, School of Medicine, Institute of Tumor Research, Chungbuk National University, Cheongju 28644, Republic of Korea
5Department of Biological Science, KI for the BioCentury, KAIST, Daejeon 34141, Republic of Korea
6Center for Plant Aging Research, Institute for Basic Science, DGIST, Daegu 42988, Republic of Korea
7Department of Pathology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea
8Present address: Hochiminh City University of Food Industry, Hochiminh city, Vietnam
These authors jointly supervised this work: Sun Hee Lee, Do Young Hyeon
*Correspondence to Daehee Hwang or You Mie Lee.
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.
논문정보
- Research article
- 2020년 10월 (BRIC 등록일 2020-11-04)
- 국내 연구진
- 생명과학 > 노화/암생물학
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