Search Results (2)

NAA10 (N-alpha-acetyltransferase 10) is a pivotal enzyme in eukaryotic cells, serving as the catalytic subunit of the NatA complex, which is responsible for the N-terminal acetylation of approximately 40–50% of the human proteome. Beyond its canonical role in co-translational N-terminal acetylation, NAA10 also acetylates internal lysine residues of various proteins and exerts non-catalytic regulatory functions through diverse protein–protein interactions. Pathogenic variants in NAA10 are linked to a spectrum of developmental disorders, most notably Ogden syndrome, which is characterized by neurodevelopmental delay, cardiac defects, and craniofacial anomalies. In cancer, NAA10 is frequently overexpressed or genomically amplified, where its dysregulation correlates with tumor aggressiveness and poor prognosis. Functional studies implicate NAA10 in regulating cell cycle progression, apoptosis, migration, and other hallmarks of cancer. In this review, we summarize the structure, molecular mechanisms, and physiological functions of NAA10, as well as its roles in human diseases and cancer. We present in silico pan-cancer analyses that highlight its clinical significance and potential downstream pathways. Furthermore, we discuss the therapeutic potential and challenges of targeting NAA10 in cancer, and propose future research directions to better understand its multifaceted roles in health and disease. Full article

Arrest defective 1 (ARD1), also known as N(alpha)-acetyltransferase 10 (NAA10) was originally identified as an N-terminal acetyltransferase (NAT) that catalyzes the acetylation of N-termini of newly synthesized peptides. After that, mammalian ARD1/NAA10 expanded its’ role to lysine acetyltransferase (KAT) that post-translationally acetylates internal lysine residues of proteins. ARD1/NAA10 is the only enzyme with both NAT and KAT activities. However, recent studies on the role of human ARD1/NAA10 (hARD1/NAA10) in lysine acetylation are contradictory, as crystal structure and in vitro acetylation assay results revealed the lack of KAT activity. Thus, the role of hARD1/NAA10 in lysine acetylation is still debating. Here, we found a clue that possibly explains these complicated and controversial results on KAT activity of hARD1/NAA10. Recombinant hARD1/NAA10 exhibited KAT activity, which disappeared soon in vitro. Size-exclusion analysis revealed that most recombinant hARD1/NAA10 formed oligomers over time, resulting in the loss of KAT activity. While oligomeric recombinant hARD1/NAA10 lost its ability for lysine acetylation, its monomeric form clearly exhibited lysine acetylation activity in vitro. We also characterized the KAT activity of hARD1/NAA10 that was influenced by several experimental conditions, including concentration of reactants and reaction time. Taken together, our study proves that recombinant hARD1/NAA10 exhibits KAT activity in vitro but only under accurate conditions, including reactant concentrations and reaction duration. Full article