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논문 기본 정보

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학술저널
저자정보
Jung Taek-Yeol (Ewha Womans University) 유재은 (이화여자대학교 세포항상성 연구센터) Jang Mi-Mi (Ewha Womans University) Lee Soh-Yeon (Ewha Womans University) Jin Gyu-Rin (Ewha Womans University) Kim Chan-Woo (Ewha Womans University) 이채영 (이화여자대학교) 김혜리 (이화여자대학교) EungHan Kim (Chungbuk National University) Park Sera (KaiPharm) Lee Seonjeong (Korea Institute of Science and Technology) Cheolju Lee (Korea Institute of Science and Technology) 김완규 (이화여자대학교) 김태수 (이화여자대학교) 이수영 (이화여자대학교) 주봉건 (서강대학교) 김현석 (이화여자대학교)
저널정보
대한생화학·분자생물학회 Experimental and Molecular Medicine Experimental and Molecular Medicine 제52권
발행연도
2020.11
수록면
1 - 14 (14page)
DOI
10.1038/s12276-020-00525-3

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N-α-acetyltransferase 20 (Naa20), which is a catalytic subunit of the N-terminal acetyltransferase B (NatB) complex, has recently been reported to be implicated in hepatocellular carcinoma (HCC) progression and autophagy, but the underlying mechanism remains unclear. Here, we report that based on bioinformatic analysis of Gene Expression Omnibus and The Cancer Genome Atlas data sets, Naa20 expression is much higher in HCC tumors than in normal tissues, promoting oncogenic properties in HCC cells. Mechanistically, Naa20 inhibits the activity of AMP-activated protein kinase (AMPK) to promote the mammalian target of rapamycin signaling pathway, which contributes to cell proliferation, as well as autophagy, through its N-terminal acetyltransferase (NAT) activity. We further show that liver kinase B1 (LKB1), a major regulator of AMPK activity, can be N-terminally acetylated by NatB in vitro, but also probably by NatB and/or other members of the NAT family in vivo, which may have a negative effect on AMPK activity through downregulation of LKB1 phosphorylation at S428. Indeed, p-LKB1 (S428) and p-AMPK levels are enhanced in Naa20-deficient cells, as well as in cells expressing the nonacetylated LKB1-MPE mutant; moreover, importantly, LKB1 deficiency reverses the molecular and cellular events driven by Naa20 knockdown. Taken together, our findings suggest that N-terminal acetylation of LKB1 by Naa20 may inhibit the LKB1?AMPK signaling pathway, which contributes to tumorigenesis and autophagy in HCC.

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