Abstract
Protein N-ɛ-acetylation is recognized as an important modification influencing many biological processes, and protein deacetylase inhibitors leading to N-ɛ-hyperacetylation of histones are being clinically tested for their potential as anticancer drugs. In contrast to N-ɛ-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.
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Acknowledgements
We thank K Jacobsen and C Hoff for excellent technical assistance. This work was supported by The Norwegian Cancer Society (Grants to TA, DG, JEV, JRL), The International Agency for Research on Cancer and The European Commission through a Marie Curie Intra-European Fellowship (Grants to FP), The Locus of Experimental Cancer Research (University of Bergen) and The Meltzer Foundation (Grant to TA).
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Arnesen, T., Gromyko, D., Pendino, F. et al. Induction of apoptosis in human cells by RNAi-mediated knockdown of hARD1 and NATH, components of the protein N-α-acetyltransferase complex. Oncogene 25, 4350–4360 (2006). https://doi.org/10.1038/sj.onc.1209469
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DOI: https://doi.org/10.1038/sj.onc.1209469
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