Identification and characterization of the human N‐acetyltransferase complexes hNatB and hNatC.

Abstract

Protein N‐alpha‐terminal acetylation is a conserved and widespread protein modification in eukaryotes. Several studies have linked it to normal cell function and cancer development, but nevertheless, little is known about its biological function. In yeast, three major complexes, NatA, NatB and NatC catalyse near all N‐alpha‐terminal acetylation, acetylating specific subsets of proteins. In humans, the NatA complex is the most extensively studied. We here present the human NatB and NatC complexes (hNatB and hNatC). They are conserved from yeast with respect to subunit composition, substrate specificity and ribosome binding. Knockdown of hNatB subunits disrupts normal cell cycle progression, and induces growth inhibition in HeLa cells and the thyroid cancer cell line CAL‐62. Knockdown of hNatC subunits results in p53‐dependent cell death and reduced growth in human cell lines. Taken together, these studies emphasize the biological importance of N‐alpha‐terminal acetylation.