Seminars

Post-translational modifications (PTMs) are chemical alterations that occur in proteins that play critical roles in various cellular functions. Lysine acetylation is an important PTM in eukaryotes, and it is catalyzed by lysine acetyltransferases (KATs). KATs transfer acetyl-coenzyme A to the internal lysine residue of substrate proteins. N-alpha-acetyltransferase 10 (NAA10) is a member of the KAT family. NAA10-mediated lysine acetylation is a key switch that regulates the enzymatic activities and biological functions of proteins.

NAA10 was first identified in Saccharomyces cerevisiae and it has N-terminal acetyltransferase activity (NAT). After that, mammalian NAA10 has been revealed to have KAT and NAT activities. In the last decade, various proteins, including HIF-1α, β-catenin, and Hsp70, have been shown to be acetylated by NAA10 at their internal lysine residues. Many studies have revealed that NAA10-mediated protein acetylation plays an important role in modulating several cellular events that are important for cancer development, such as cell cycle progression, cell death, and migration. On the basis of this evidence, targeting of NAA10 has been proposed as a promising avenue for the development of novel cancer therapeutics. 

In this study, we found that NAA10 promotes cancer cell growth by acetylation of protein arginine methyltransferase 5 (PRMT5). PRMT5 is one of the protein arginine methyltransferases (PRMTs), which catalyze the transfer of one or two methyl groups to the guanidine nitrogen atoms of arginine. PRMT5 is an essential enzyme involved in a variety of biological processes such as tumorigenesis, transcription, differentiation and spliceosome assembly via histone and other proteins methylation, however little is known about its regulatory mechanisms. Here, we found that PRMT5 is acetylated by NAA10 and this modification is essential for functional activation of PRMT5. Inhibition of PRMT5 acetylation abolished the ability of PRMT5 to methylate histone H4 and to promote cancer cell growth. Based on these results, we suggest that NAA10-mediated lysine acetylation is a key switch that regulates the enzymatic activities and biological functions of PRMT5 and inhibition of PRMT5 acetylation could be a potential way to control tumor development.