Disease relevance of ARD1A

• In H1299 and A549 lung cancer cells, hARD1-silencing RNA inhibited cell proliferation and induced G(1) arrest [1].
• Analysis of ARD1 function in hypoxia response using retroviral RNA interference [2].
• In addition, we show that the ARD1 mRNA and protein levels are not regulated by hypoxia in several human tumor cell lines, including cervical adenocarcinoma HeLa cells, fibrosarcoma HT1080 cells, adenovirus-transformed human kidney HEK293 cells, and human breast cancer MCF-7 cells [3].
• Expression of HIF-1alpha and VEGF was examined in two oesophageal squamous cell carcinoma cell lines (TE2, TE3) and 82 archival surgical specimens of human oesophageal squamous cell carcinoma tissue [4].
• EXPERIMENTAL DESIGN AND RESULTS: Microarray analysis was applied to verify the gene expression profiles of 4,608 genes after FK228 treatment using human esophageal squamous cell cancer cell lines T.Tn and TE2 [5].

High impact information on ARD1A

• Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation [6].
• Therefore, it is suggested that hARD1 participates in proliferation of lung cancer cells via the activation of beta-catenin [1].
• Arrest defective 1 (ARD1), an acetyltransferase, is essential for the yeast life cycle [1].
• In addition to the HIF proline hydroxylases and asparagine hydroxylases, ARD1 is recently described as a HIF-1alpha acetylase that regulates its stability [2].
• After surveying these lines for erythropoietin production and retroviral transfection efficiency, we chose to use HepG2 cells to study the function of ARD1 [2].

Biological context of ARD1A

• Characterization of hARD2, a processed hARD1 gene duplicate, encoding a human protein N-alpha-acetyltransferase [7].
• The beta-catenin binding and acetylation by hARD1 were observed in vitro [1].
• Induction of apoptosis in human cells by RNAi-mediated knockdown of hARD1 and NATH, components of the protein N-alpha-acetyltransferase complex [8].
• Our results argue for an essential role of the NATH-hARD1 complex in cell survival and underscore the importance of protein N-alpha-acetylation in mammalian cells [8].
• The role of ARD1 in cell proliferation is confirmed using fluorescence labeling analysis of cell division [2].

Anatomical context of ARD1A

• Here, we demonstrate that knockdown of NATH and/or hARD1 triggers apoptosis in human cell lines [8].
• We also demonstrate that ARD1 is a stable, predominantly cytoplasmic protein expressed in a broad range of tissues, tumor cell lines, and endothelial cells [3].
• RESULTS: In normal subjects, tendon stimulation elicited an excitatory phase (TE1), followed by a pronounced inhibitory phase (TI1) and a second excitatory phase (TE2) [9].
• METHODS: Cancer cell lines from the lung (H460, H322), the esophagus (TE2, TE12), and the pleura (H290, H211) or primary normal cells were treated with gossypol+Apo2L/TRAIL combinations [10].

Associations of ARD1A with chemical compounds

• In addition, hARD1 forms protofilaments under physiological conditions of pH and temperature, as judged by electron microscopy and staining with the dyes Congo red and thioflavin T [11].
• 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 [7].
• Knockdown of hARD1 also sensitized cells to daunorubicin-induced apoptosis, potentially pointing at the NATH-hARD1 acetyltransferase complex as a novel target for chemotherapy [8].
• In contrast, the growth of TE2/TK tumors was significantly inhibited by GCV and all the tumors disappeared [12].
• DESIGN, SETTING AND METHODS: We analysed total estrogen (TE) and testosterone (TT) levels in women diagnosed with AD and controls of the Oxford Project To Investigate Memory and Ageing. Because estradiol (TE2) after the menopause is largely derived from estrone (TE1), we computed the ratio TE2/(TE1+TE2) and a total steroid index (TT+TE2+TE1) [13].

Analytical, diagnostic and therapeutic context of ARD1A

• Structural characterization of native hARD1 using size exclusion chromatography, circular dichroism, and fluorescence spectroscopy shows the protein consists of a compact globular region comprising two thirds of the protein and a flexible unstructured C terminus [11].
• A gene chip analysis of HepG2 cells transduced with virus expressing ARD1 short hairpin RNA under normoxia and hypoxia conditions or with virus overexpressing recombinant ARD1 confirmed that inhibition of ARD1 does not cause activation of HIF and downstream target genes [2].
• Cells were transiently transfected with HIF-1alpha mutant and antisense arrest-defective 1 protein (ARD-1), and HIF-1alpha acetylation was assayed by immunoprecipitation [14].
• In mouse xenograft models of T.Tn and TE2 cells, FK228 injection resulted in significant tumor regression as well as activated Prdx1 expression in tumor tissues [5].
• EXPERIMENTAL DESIGN: TE-2 proteins were separated by two-dimensional PAGE, followed by Western blot analysis in which sera of patients with ESCC, healthy controls, and patients with other cancers were tested for primary antibodies [15].

References