Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apolipoprotein B (ApoB) is a major constituent of the plasma lipoproteins. In adult mammals it is synthesized in two different tissues, liver and intestine. We have examined the promoter elements involved in determining the cell specificity of apoB expression, using a chloramphenicol acetyltransferase assay and the cell lines HepG2, CaCo-2 and HeLa. The human apoB promoter contains: (i) a strong, cell-specific, positive element which can act on a heterologous promoter. This element is located between pos -111 and -33 and is built up by three subdomains, two positive and one negative; (ii) a large, negative element between pos -639 and -129, which reduces promoter activity in apoB expressing cells (HepG2 and CaCo-2) and block activation of the promoter by the SV40 enhancer in non-expressing cells (HeLa); (iii) a positive element in the noncoding part of exon 1 which retains its activity if placed upstream from the other regulatory elements and stimulates transcription from the simian virus 40 promoter in all three cell lines. The same sequence elements appear to be important for expression in cells of hepatic (HepG2) and intestinal (CaCo-2) origin.
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PMID:Negative and positive promoter elements contribute to tissue specificity of apolipoprotein B expression. 250 Nov 59

Apolipoprotein B (apoB) is required for the assembly and secretion of triglyceride-rich lipoproteins. ApoB synthesis is constitutive, and post-translational mechanisms modulate its secretion. Transforming growth factor beta (TGF-beta) increased apoB secretion in both differentiated and nondifferentiated Caco-2 cells and decreased secretion in HepG2 cells without affecting apolipoprotein A-I secretion. TGF-beta altered apoB secretion by changing steady-state mRNA levels and protein synthesis. Expression of SMAD3 and SMAD4 differentially regulated apoB secretion in these cells. Thus, SMADs mediate dissimilar secretion of apoB in both the cell lines by affecting gene transcription. We identified a 485-bp element, 55 kb upstream of the apob gene that contains a SMAD binding motif. This motif increased the expression of chloramphenicol acetyltransferase in Caco-2 cells treated with TGF-beta or transfected with SMADs. Hence, TGF-beta activates SMADs that bind to the 485-bp intestinal enhancer element in the apob gene and increase its transcription and secretion in Caco-2 cells. This is the first example showing differential transcriptional regulation of the apob gene by cytokines and dissimilar regulation of one gene in two different cell lines by TGF-beta. In this regulation, the presence of cytokine-responsive motif in the tissue-specific enhancer element confers cell-specific response.
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PMID:Differential, tissue-specific, transcriptional regulation of apolipoprotein B secretion by transforming growth factor beta. 1217 61

The X protein of hepatitis B virus (HBx) plays a major role on hepatocellular carcinoma (HCC). Apolipoprotein B (apoB) in the liver is an important glycoprotein for transportation of very low density lipoproteins and low density lipoproteins. Although lipid accumulation in the liver is known as one of the factors for the HCC, the relationship between HBx and apoB during the HCC development is poorly understood. To better understand the biological significance of HBx in HCC, liver Chang cells that specifically express HBx were established and characterized. In this study we demonstrate that overexpression of HBx significantly up-regulates the expression of UDP-N-acetylglucosamine:beta-d-mannoside-1,4-N-acetylglucosaminyltransferase-III (GnT-III), an enzyme that functions as a bisecting-N-acetylglucosamine (GlcNAc) transferase in apoB, and increases GnT-III promoter activity in a chloramphenicol acetyltransferase assay. GnT-III expression levels of HBx-transfected cells appeared to be higher than that of hepatocarcinoma cells as well as GnT-III-transfected cells, indicating that HBx may has a strong GnT-III promotor-enhancing activity. Intracellular levels of apoBs, which contained the increased bisecting GlcNAc, were accumulated in HBx-transfected liver cells. These cells as well as GnT-III-transfected liver cells revealed the inhibition of apoB secretion and the increased accumulation of intracellular triglyceride and cholesterol compared with vector-transfected cells. Moreover, overexpression of GnT-III and HBx in liver cells was shown to down-regulate the transcriptional level of microsomal triglyceride transfer protein, which regulates the assembly and secretion of apoB. Therefore, our study strongly suggested that the HBx increase in intracellular accumulation of aberrantly glycosylated apoB resulted in inhibition of secretion of apoB as well as intracellular lipid accumulation by elevating the expression of GnT-III.
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PMID:The hepatitis B virus X protein inhibits secretion of apolipoprotein B by enhancing the expression of N-acetylglucosaminyltransferase III. 1512 6