N-terminal acetylation is catalyzed by a highly conserved family of N-terminal acetyltransferases (NATs). NATs activity is mostly mediated by five distinct but highly conserved complexes (NatA to NatE) bearing distinct subunits and having different substrate specificities. Additionally, we recently identified NatF, a higher eukaryote-specific NAT complex whose enzymatic activity was responsible for a significant shift in the proteome N-terminal acetylation status. Little is still known regarding the biological significance of N-terminal acetylation in the context of a developing multicellular organism. Studying the role of N-terminal acetylation during development will likely contribute to a better understanding of carcinogenesis, as NATs expression is frequently misregulated in aggressive or advanced tumors.
We and others have shown that N-terminal acetylation is important for the correct segregation of chromosomes during mitosis. The gene separation anxiety (san) encodes Naa50/ San, a conserved N-terminal acetyltransferase defined as NatE. Drosophila and human HeLa cells mutant for Naa50/ San show chromosome segregation defects during mitosis, including lagging chromosomes and chromatid bridges. We defined the substrate consensus sequence of Naa50/ San and we hypothesize that Naa50/ San acetylates a protein involved in chromosome segregation. Consistent with this hypothesis, ongoing work suggests that Drosophila Naa50/ San is required for N-terminal acetylation of a highly conserved protein essential for chromosome segregation. Interestingly, and in contrast to all tested somatic cells, Naa50/ San is not required for mitosis within the germline stem cells, which suggests differential regulation of protein N-terminal acetylation between the soma and the germline. We hypothesize that such differential regulation is important for the correct development of the germline.