Protein acetyltransferases and deacetylases have been implicated in
oncogenesis, apoptosis and cell cycle regulation. Most of the
protein acetyltransferases described acetylate epsilon-amino groups of
lysine residues within
proteins. Mouse ARD1 (homologue of yeast Ard1p, where Ard1p stands for arrest defective 1
protein) is the only known
protein acetyltransferase catalysing acetylation of
proteins at both alpha-(N-terminus) and epsilon-amino groups. Yeast Ard1p interacts with Nat1p (
N-acetyltransferase 1 protein) to form a functional
NAT (N-
acetyltransferase). We now describe the human homologue of Nat1p, NATH (
NAT human), as the partner of the hARD1 (human ARD1)
protein. Included in the characterization of the NATH and hARD1
proteins is the following: (i) endogenous NATH and hARD1
proteins are expressed in human epithelial,
glioma and promyelocytic cell lines; (ii) NATH and hARD1 form a stable complex, as investigated by reciprocal immunoprecipitations followed by MS analysis; (iii) NATH-hARD1 complex expresses N-terminal acetylation activity; (iv) NATH and hARD1 interact with ribosomal subunits, indicating a co-translational
acetyltransferase function; (v) NATH is localized in the cytoplasm, whereas hARD1 localizes both to the cytoplasm and nucleus; (vi) hARD1 partially co-localizes in nuclear spots with the
transcription factor HIF-1alpha (
hypoxia-inducible factor 1alpha), a known epsilon-amino substrate of ARD1; (vii) NATH and hARD1 are cleaved during apoptosis, resulting in a decreased
NAT activity. This study identifies the human homologues of the yeast Ard1p and Nat1p
proteins and presents new aspects of the NATH and hARD1
proteins relative to their yeast homologues.