Naa20, the catalytic subunit of NatB complex, contributes to hepatocellular carcinoma by regulating the LKB1–AMPK–mTOR axis

Taek Yeol Jung, Jae Eun Ryu, Mi Mi Jang, Soh Yeon Lee, Gyu Rin Jin, Chan Woo Kim, Chae Young Lee, Hyelee Kim, Eung Han Kim, Sera Park, Seonjeong Lee, Cheolju Lee, Wankyu Kim, Tae Soo Kim, Soo Young Lee, Bong Gun Ju, Hyun Seok Kim

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1 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1831-1844
Number of pages14
JournalExperimental and Molecular Medicine
Volume52
Issue number11
DOIs
StatePublished - Nov 2020

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