Characterization of hARD2, a processed hARD1 gene duplicate, encoding a human protein N-α-acetyltransferase

Department of Molecular Biology, University of Bergen, N-5020 Bergen, Norway.
BMC Biochemistry (Impact Factor: 1.44). 02/2006; 7(1):13. DOI: 10.1186/1471-2091-7-13
Source: PubMed


Protein acetylation is increasingly recognized as an important mechanism regulating a variety of cellular functions. Several human protein acetyltransferases have been characterized, most of them catalyzing epsilon-acetylation of histones and transcription factors. We recently described the human protein acetyltransferase hARD1 (human Arrest Defective 1). hARD1 interacts with NATH (N-Acetyl Transferase Human) forming a complex expressing protein N-terminal alpha-acetylation activity.
We here describe a human protein, hARD2, with 81 % sequence identity to hARD1. The gene encoding hARD2 most likely originates from a eutherian mammal specific retrotransposition event. hARD2 mRNA and protein are expressed in several human cell lines. Immunoprecipitation experiments show that hARD2 protein potentially interacts with NATH, suggesting that hARD2-NATH complexes may be responsible for protein N-alpha-acetylation in human cells. In NB4 cells undergoing retinoic acid mediated differentiation, the level of endogenous hARD1 and NATH protein decreases while the level of hARD2 protein is stable.
A human protein N-alpha-acetyltransferase is herein described. ARD2 potentially complements the functions of ARD1, adding more flexibility and complexity to protein N-alpha-acetylation in human cells as compared to lower organisms which only have one ARD.

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Available from: Thomas Arnesen, Aug 14, 2015
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    • "NATH (N-acetyl transferase human) is involved in protein acetylation which represents an important post-translational modification regulating oncogenesis, apoptosis and cell cycle. NATH resulted to be over-expressed at the mRNA level in papillary thyroid carcinomas compared to non-neoplastic thyroid tissue [8]. "
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    ABSTRACT: Background Thyroid nodules with indeterminate cytological features on fine needle aspiration (FNA) cytology have a 20% risk of thyroid cancer. The aim of the current study was to determine the diagnostic utility of an 8-gene assay to distinguish benign from malignant thyroid neoplasm. Methods The mRNA expression level of 9 genes (KIT, SYNGR2, C21orf4, Hs.296031, DDI2, CDH1, LSM7, TC1, NATH) was analysed by quantitative PCR (q-PCR) in 93 FNA cytological samples. To evaluate the diagnostic utility of all the genes analysed, we assessed the area under the curve (AUC) for each gene individually and in combination. BRAF exon 15 status was determined by pyrosequencing. An 8-gene computational model (Neural Network Bayesian Classifier) was built and a multiple-variable analysis was then performed to assess the correlation between the markers. Results The AUC for each significant marker ranged between 0.625 and 0.900, thus all the significant markers, alone and in combination, can be used to distinguish between malignant and benign FNA samples. The classifier made up of KIT, CDH1, LSM7, C21orf4, DDI2, TC1, Hs.296031 and BRAF had a predictive power of 88.8%. It proved to be useful for risk stratification of the most critical cytological group of the indeterminate lesions for which there is the greatest need of accurate diagnostic markers. Conclusion The genetic classification obtained with this model is highly accurate at differentiating malignant from benign thyroid lesions and might be a useful adjunct in the preoperative management of patients with thyroid nodules.
    BMC Cancer 09/2012; 12(1):396. DOI:10.1186/1471-2407-12-396 · 3.36 Impact Factor
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    • "hNaa11p (hArd2) display 81% sequence identity to hNaa10p, and hNAA11 is the result of a mammal-specific retrotransposition event, making hNAA11 a gene duplicate of hNAA10. Exogenous hNaa11p displays Nα-acetyltransferase activity and forms putative hNatA complexes in association with hNaa15p and hNaa16p [11,12]. The hNAA11 mRNA is moderately expressed in most tissues, and its function is largely unknown. "
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    ABSTRACT: Protein Nalpha-terminal acetylation is one of the most common protein modifications in eukaryotic cells, occurring on approximately 80% of soluble human proteins. An increasing number of studies links Nalpha-terminal acetylation to cell differentiation, cell cycle, cell survival, and cancer. Thus, Nalpha-terminal acetylation is an essential modification for normal cell function in humans. Still, little is known about the functional role of Nalpha-terminal acetylation. Recently, the three major human N-acetyltransferase complexes, hNatA, hNatB and hNatC, were identified and characterized. We here summarize the identified N-terminal acetyltransferase complexes in humans, and we review the biological studies on Nalpha-terminal acetylation in humans and other higher eukaryotes.
    BMC proceedings 02/2009; 3 Suppl 6(Suppl 6):S3. DOI:10.1186/1753-6561-3-S6-S3
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    • "hNaa10p and/or hNaa15p has been demonstrated to be important for cell survival [6-8] suggesting important functions for hNaa10p or hNatA mediated acetylation in human cells. In humans, there are two paralogues for each NatA subunit, hNaa10p and hNaa11p [9], and hNaa15p and hNaa16p (Arnesen et al., submitted), potentially creating a more flexible and complex system for NatA mediated N-terminal acetylation as compared to lower eukaryotes. "
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    ABSTRACT: The hNaa10p (hArd1) protein is the catalytic subunit of the human NatA Nalpha-terminal acetyltransferase complex. The NatA complex is associated with ribosomes and cotranslationally acetylates human proteins with Ser-, Ala-, Thr-, Val-, and Gly- N-termini after the initial Met- has been removed. In the flexible C-terminal tail of hNaa10p, there are several potential phosphorylation sites that might serve as points of regulation. Using 2D-gel electrophoresis and hNaa10p specific antibodies, we have investigated whether hNaa10p is phosphorylated in HEK293 cells. Several differently charged forms of hNaa10p are present in HEK293 cells and treatment with Calf Intestine Alkaline Phophatase (CIAP) strongly suggests that hNaa10p is phosphorylated at multiple sites under various cell culture conditions. A direct or indirect role of GSK-3 kinase in regulating hNaa10p phosphorylation is supported by the observed effects of Wortmannin and LiCl, a GSK-3 activator and inhibitor, respectively. We demonstrate that hNaa10p protein is phosphorylated in cell culture potentially pointing at phosphorylation as a means of regulating the function of one of the major Nalpha-terminal acetyltransferases in human cells.
    BMC Research Notes 02/2009; 2(1):32. DOI:10.1186/1756-0500-2-32
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