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

Experimental & Molecular Medicine
Taek-Yeol JungHyun-Seok Kim

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,...Continue Reading

References

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Citations

Jun 22, 2021·Frontiers in Oncology·Costas Koufaris, Antonis Kirmizis

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Datasets Mentioned

BETA
GSE54236
GSE36376

Methods Mentioned

BETA
acetylation
transfection
electrophoresis
immunoprecipitation
protein assay
RNA-Seq
fluorescence microscopy
Fluorescence

Software Mentioned

R
PDV
Bioconductor
GenomicDataCommons
GEOquery R
image
SEQUEST ( Proteome Discoverer

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