Correlation of Expression of Human Arrest-Defective-1 (hARD1) Protein With Breast Cancer

Laboratory of Biochemistry and Molecular Biology, School of Life Science, Yunnan University, Kunming, China.
Cancer Investigation (Impact Factor: 2.22). 12/2009; 27(10):978-83. DOI: 10.3109/07357900902769723
Source: PubMed


Human arrest-defective-1 (hARD1) was reported to be important in regulating cell cycle and promoting lung cancer cell proliferation. Here we have investigated the correlation between hARD1 and breast cancer. Analysis with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry (FCM) demonstrated that overexpression of hARD1 was associated with increased proliferation of MCF-7 cell, a human breast cancer cell line. Western blotting and immunohistochemical staining assay showed that hARD1 presented higher in breast cancer tissue than the adjacent tissue; accumulation of hARD1 protein was higher in 86% (37/43) of breast cancer, far more than noncancer samples. Our results suggest that hARD1 might play an important role in breast cancer carcinogenesis.

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    • "In addition to histones, over 200 proteins are acetylated in eukaryotes, which are important for a variety of processes [9]. One representative example of an acetyltransferase is human N-acetyltransferase Ard1 (hArd1) which was overexpressed in various cancer cells and tissues such as hepatocellular carcinoma [12], colorectal cancer [13] [14], lung cancer [14] [15], urinary bladder cancer [14], cervical carcinoma, and breast cancer [14] [16]. "
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    ABSTRACT: Acetylation and deacetylation reactions result in biologically important modifications that are involved in normal cell function and cancer development. These reactions, carried out by protein acetyltransferase enzymes, act by transferring an acetyl group from acetyl-coenzyme A (Ac-CoA) to various substrate proteins. Such protein acetylation remains poorly understood in Archaea, and has been only partially described. Information processing in Archaea has been reported to be similar to that in eukaryotes and distinct from the equivalent bacterial processes. The human N-acetyltransferase Ard1 (hArd1) is one of the acetyltransferases that has been found to be overexpressed in various cancer cells and tissues, and knockout of the hArd1 gene significantly reduces growth rate of the cancer cell lines. In the present study, we determined the crystal structure of Thermoplasma volcanium Ard1 (Tv Ard1), which shows both ligand-free and multiple ligand-bound forms, i.e., Ac-CoA- and coenzyme A (CoA) -bound forms. The difference between ligand-free and ligand-bound chains in the crystal structure was used to search for the interacting residues. The re-orientation and position of the loop between β4 and α3 including the phosphate-binding loop (P-loop) were observed, which are important for the ligand interaction. In addition, a biochemical assay to determine the N-acetyltransferase activity of Tv Ard1 was performed using the Thermoplasma volcanium substrate protein Alba (Tv Alba). Taken together, the findings of this study elucidate ligand-free form of Tv Ard1 for the first time and suggest multiple modes of binding with Ac-CoA and CoA.
    Biochimica et Biophysica Acta (BBA) - Proteins & Proteomics 10/2014; 1844(10). DOI:10.1016/j.bbapap.2014.07.011 · 2.75 Impact Factor
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    • "Further studies have shown that ARD1 is present in various species, including the mouse, rat, chimpanzee, and human, and has several variants, playing different roles [3]–[6]. In humans, human ARD1235 (hARD1) is the major form, involved in diverse biological processes, such as cell proliferation, differentiation, autophagy, and cancer [7]–[13]. "
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    ABSTRACT: Arrest defective 1 (ARD1) is an acetyltransferase that is highly conserved across organisms, from yeasts to humans. The high homology and widespread expression of ARD1 across multiple species and tissues signify that it serves a fundamental role in cells. Human ARD1 (hARD1) has been suggested to be involved in diverse biological processes, and its role in cell proliferation and cancer development has been recently drawing attention. However, the subcellular localization of ARD1 and its relevance to cellular function remain largely unknown. Here, we have demonstrated that hARD1 is imported to the nuclei of proliferating cells, especially during S phase. Nuclear localization signal (NLS)-deleted hARD1 (hARD1ΔN), which can no longer access the nucleus, resulted in cell morphology changes and cellular growth impairment. Notably, hARD1ΔN-expressing cells showed alterations in the cell cycle and the expression levels of cell cycle regulators compared to hARD1 wild-type cells. Furthermore, these effects were rescued when the nuclear import of hARD1 was restored by exogenous NLS. Our results show that hARD1 nuclear translocation mediated by NLS is required for cell cycle progression, thereby contributing to proper cell proliferation.
    PLoS ONE 08/2014; 9(8):e105185. DOI:10.1371/journal.pone.0105185 · 3.23 Impact Factor
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    • "Whether or not there is any functional association between these pathways and PA28-regulated chymotrypsin-like proteasome activity still needs more considerations. It was reported that overexpression of Naa10p may serve as a prognostic factor in different cancers [7] [10] [15] [16] [33]. Overexpression of PA28b was found in gastric adenocarcinomas, though its prognostic value still needs exploration [34] [35]. "
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    ABSTRACT: N-α-acetyltransferase 10 protein (Naa10p) regulates various pathways associated with cancer cell proliferation, metastasis, apoptosis and autophagy. However, its role in protein quality control is unknown. Here, we report that Naa10p is physically associated with proteasome activator 28β (PA28β). Naa10p also interacts with PA28α in a PA28β-dependent manner. Naa10p negatively regulates PA28-dependent chymotrypsin-like proteasome activity in cancer cells and in a cell-free system reconstituted with purified proteins, which was not related to 26S proteasome. Acetyltransferase activity of Naa10p isn't required for its effect on chymotrypsin-like proteasome activity. Therefore, our data reveal that Naa10p suppresses 28S proteasome activity through interaction with PA28β. STRUCTURED SUMMARY OF PROTEIN INTERACTIONS: Naa10pphysically interactswithPS28alphaandPS28 betabyanti bait coimmunoprecipitation(View Interaction:1,2).
    FEBS letters 04/2013; 587(11). DOI:10.1016/j.febslet.2013.04.016 · 3.17 Impact Factor
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