title: Identification and characterization of the human ARD1-NATH protein acetyltransferase complex.
abstract: 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.
authors.affiliation: Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway.
authors.forename: Thomas
authors.initials: T
authors.lastname: Arnesen
authors.forename: Dave
authors.initials: D
authors.lastname: Anderson
authors.forename: Christian
authors.initials: C
authors.lastname: Baldersheim
authors.forename: Michel
authors.initials: M
authors.lastname: Lanotte
authors.forename: Jan E
authors.initials: JE
authors.lastname: Varhaug
authors.forename: Johan R
authors.initials: JR
authors.lastname: Lillehaug
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D017209:Apoptosis; D001665:Binding Sites; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D019204:GTP-Binding Proteins; D006801:Humans; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D063209:N-Terminal Acetyltransferase A; D063213:N-Terminal Acetyltransferase E; D009363:Neoplasm Proteins / Q000737:chemistry / Q000378:metabolism*; D011132:Polyribosomes / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface
chemical_list: D046912:Multiprotein Complexes; C463022:NAA15 protein, human; D009363:Neoplasm Proteins; C419368:RACK1 protein, human; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D000123:Acetyltransferases; C061313:protein N-terminal acetyltransferase; D063209:N-Terminal Acetyltransferase A; D063213:N-Terminal Acetyltransferase E; D019204:GTP-Binding Proteins