Induction of apoptosis in human cells by RNAi-mediated knockdown of hARD1 and NATH, components of the protein N-α-acetyltransferase complex

Arnesen, T
Gromyko, D
Pendino, F
Ryningen, A
Varhaug, J E
Lillehaug, J R

¹Department of Molecular Biology, University of Bergen, Bergen, Norway; ²Department of Surgical Sciences, University of Bergen and Haukeland University Hospital, Bergen, Norway; ³Department of Medicine, Haukeland University Hospital, Bergen, Norway

Oncogene (2006) 25, 4350-4360. doi:10.1038/sj.onc.1209469

Correspondence: Dr T Arnesen, Department of Molecular Biology, University of Bergen, Thormohlensgate 55, Bergen High Technology Center, N-5020 Bergen, Norway. E-mail: [email protected]

⁴These authors contributed equally.

Received 15 August 2005; revised 11 January 2006; accepted 24 January 2006; published online 6 March 2006

Oncogene 25(31):p 4350-4360, July 20, 2006.

Protein N-ε-acetylation is recognized as an important modification influencing many biological processes, and protein deacetylase inhibitors leading to N-ε-hyperacetylation of histones are being clinically tested for their potential as anticancer drugs. In contrast to N-ε-acetyltransferases, the N-α-acetyltransferases transferring acetyl groups to the α-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-α-acetylation in mammalian cells.