The Human N-Alpha-Acetyltransferase 40 (hNaa40p/hNatD) Is Conserved from Yeast and N-Terminally Acetylates Histones H2A and H4

Ludwig-Maximilians-Universität München, Germany
PLoS ONE (Impact Factor: 3.23). 09/2011; 6(9):e24713. DOI: 10.1371/journal.pone.0024713
Source: PubMed


Protein Nα-terminal acetylation (Nt-acetylation) is considered one of the most common protein modification in eukaryotes, and 80-90% of all soluble human proteins are modified in this way, with functional implications ranging from altered protein function and stability to translocation potency amongst others. Nt-acetylation is catalyzed by N-terminal acetyltransferases (NATs), and in yeast five NAT types are identified and denoted NatA-NatE. Higher eukaryotes additionally express NatF. Except for NatD, human orthologues for all yeast NATs are identified. yNatD is defined as the catalytic unit Naa40p (Nat4) which co-translationally Nt-acetylates histones H2A and H4.

Download full-text


Available from: Petra Van Damme
  • Source
    • "In humans, NatA, NatB and NatC have been identified and reported to function in translation initiation as well as other events in the cell. NatD is a specific N-terminal acetyltransferase of histone H4 and H2A [20]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Mdm20 is an auxiliary subunit of the NatB complex, which includes Nat5, the catalytic subunit for protein N-terminal acetylation. The NatB complex catalyzes N-acetylation during de novo protein synthesis initiation; however, recent evidence from yeast suggests that NatB also affects post-translational modification of tropomyosin, which is involved in intracellular sorting of aggregated proteins. We hypothesized that an acetylation complex such as NatB may contribute to protein clearance and/or proteostasis in mammalian cells. Using a poly glutamine (polyQ) aggregation system, we examined whether the NatB complex or its components affect protein aggregation in rat primary cultured hippocampal neurons and HEK293 cells. The number of polyQ aggregates increased in Mdm20 over-expressing (OE) cells, but not in Nat5-OE cells. Conversely, in Mdm20 knockdown (KD) cells, but not in Nat5-KD cells, polyQ aggregation was significantly reduced. Although Mdm20 directly associates with Nat5, the overall cellular localization of the two proteins was slightly distinct, and Mdm20 apparently co-localized with the polyQ aggregates. Furthermore, in Mdm20-KD cells, a punctate appearance of LC3 was evident, suggesting the induction of autophagy. Consistent with this notion, phosphorylation of Akt, most notably at Ser473, was greatly reduced in Mdm20-KD cells. These results demonstrate that Mdm20, the so-called auxiliary subunit of the translation-coupled protein N-acetylation complex, contributes to protein clearance and/or aggregate formation by affecting the phosphorylation level of Akt indepenently from the function of Nat5.
    Full-text · Article · Dec 2013 · PLoS ONE
  • Source
    • "When the initiator methionine is followed by Asp, Glu, or Gln, it can be acetylated by NatB. NatC acetylates initiator methionines followed by hydrophobic amino acids (Leu, Ile, Tyr, or Phe), NatD acetylates the N-termini of the histones H2A and H4, and NatE acetylates proteins where the initiator methionine is followed by Leu, Ala, Lys, or Met (Polevoda et al. , 2009 ; Hole et al. , 2011 ). Finally, the recently discovered NatF, which is specifi c for higher eukaryotes, acetylates N-termini mainly starting with Met followed by Lys, Leu, Ile, Trp, or Phe (Van Damme et al. , 2011c ). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Protein N-terminal acetylation by Nα-acetyltransferases (NATs) is an omnipresent protein modification that affects a large number of proteins. The exact biological role of N-terminal acetylation has, however, remained enigmatic for the overall majority of affected proteins, and only for a rather small number of proteins, N-terminal acetylation was linked to various protein features including stability, localization, and interactions. This minireview tries to summarize the recent progress made in understanding the functionality of N-terminal protein acetylation and also focuses on noncanonical functions of the NATs subunits.
    Full-text · Article · Mar 2012 · Biological Chemistry
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The human N-terminal acetyltransferases (NATs) catalyze the transfer of acetyl moieties to the N-termini of 80-90% of all human proteins. Six NAT types are present in humans, NatA-NatF, each is composed of specific subunits and each acetylates a set of substrates defined by the N-terminal amino-acid sequence. NATs have been suggested to act as oncoproteins as well as tumor suppressors in human cancers, and NAT expression may be both elevated and decreased in cancer versus non-cancer tissues. Manipulation of NATs in cancer cells induced cell-cycle arrest, apoptosis or autophagy, implying that these enzymes target a variety of pathways. Of particular interest is hNaa10p (human ARD1), the catalytic subunit of the NatA complex, which was coupled to a number of signaling molecules including hypoxia inducible factor-1α, β-catenin/cyclin D1, TSC2/mammalian target of rapamycin, myosin light chain kinase , DNA methyltransferase1/E-cadherin and p21-activated kinase-interacting exchange factors (PIX)/Cdc42/Rac1. The variety of mechanistic links where hNaa10p acts as a NAT, a lysine acetyltransferase or displaying a non-catalytic role, provide insights to how hNaa10p may act as both a tumor suppressor and oncoprotein.Oncogene advance online publication, 5 March 2012; doi:10.1038/onc.2012.82.
    Full-text · Article · Mar 2012 · Oncogene
Show more