title: Induction of apoptosis in human cells by RNAi-mediated knockdown of hARD1 and NATH, components of the protein N-alpha-acetyltransferase complex.
abstract: Protein N-epsilon-acetylation is recognized as an important modification influencing many biological processes, and protein deacetylase inhibitors leading to N-epsilon-hyperacetylation of histones are being clinically tested for their potential as anticancer drugs. In contrast to N-epsilon-acetyltransferases, the N-alpha-acetyltransferases transferring acetyl groups to the alpha-amino groups of protein N-termini have only been briefly described in mammalians. Human arrest defective 1 (hARD1), the only described human enzyme in this class, complexes with N-acetyltransferase human (NATH) and cotranslationally transfers acetyl groups to the N-termini of nascent polypeptides. Here, we demonstrate that knockdown of NATH and/or hARD1 triggers apoptosis in human cell lines. Knockdown of hARD1 also sensitized cells to daunorubicin-induced apoptosis, potentially pointing at the NATH-hARD1 acetyltransferase complex as a novel target for chemotherapy. Our results argue for an essential role of the NATH-hARD1 complex in cell survival and underscore the importance of protein N-alpha-acetylation in mammalian cells.
authors.affiliation: Department of Molecular Biology, University of Bergen, Norway. thomas.arnesen@mbi.uib.no
authors.forename: T
authors.initials: T
authors.lastname: Arnesen
authors.forename: D
authors.initials: D
authors.lastname: Gromyko
authors.forename: F
authors.initials: F
authors.lastname: Pendino
authors.forename: A
authors.initials: A
authors.lastname: Ryningen
authors.forename: J E
authors.initials: JE
authors.lastname: Varhaug
authors.forename: J R
authors.initials: JR
authors.lastname: Lillehaug
mesh_terms: D000123:Acetyltransferases / Q000172:deficiency / Q000235:genetics*; D017209:Apoptosis / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D063209:N-Terminal Acetyltransferase A; D063213:N-Terminal Acetyltransferase E; D034622:RNA Interference
chemical_list: C463022:NAA15 protein, human; D000123:Acetyltransferases; C061313:protein N-terminal acetyltransferase; D063209:N-Terminal Acetyltransferase A; C504824:NAA10 protein, human; D063213:N-Terminal Acetyltransferase E