Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of glycosylation on the secretion and the stability of human corticosteroid binding globulin (CBG) was studied. Cells of the human hepatoma line were labeled by [35S]methionine in presence of or absence of tunicamycin (TM). Media or cells were harvested at 0, 3, 6, and 20 h after the addition of excess unlabeled methionine. Media and cell lysates were incubated with anti-CBG serum and immune complexes were precipitated with Staphylococcus aureus protein A (Pansorbin). Immunoprecipitates were analyzed by fluorography after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Immunoprecipitation of T4-binding globulin (TBG) was also carried out with anti-TBG serum. Fluorographic analysis revealed three forms of CBG: CBG1, a glycosylated, mature, and secretory form with apparent mol wt of 70 K; CBG2, a glycosylated precursor which due to incomplete carbohydrate processing has an apparent mol wt of 54 K; and CBG3, a nonglycosylated form consisting of the 40 K core protein. In absence of TM, CBG1 was observed in media and CBG2 was detected in cell lysates. The proportion of CBG1 increased during the chase, whereas that of CBG2 decreased, indicating that CBG was secreted after processing of the oligosaccharides on CBG2. In presence of TM, CBG3 was found both in media and cell lysates. The sum of CBG3 in the medium and the cell lysate decreased during the chase, whereas that of CBG1 and CBG2 remained unchanged. Similar to CBG, TBG1 (mature form, 60 K) and TBG2 (partially processed glycosylated form, 54 K) were observed in media and cell lysates, respectively, in absence of TM. However, TBG3 (nonglycosylated, 44 K) was not detected in medium. These results indicate that glycosylation is not a key factor for the secretion of CBG but is important for its stability. On the other hand the glycosylation is indispensable for the secretion of TBG.
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PMID:Studies on the role of glycosylation for human corticosteroid-binding globulin: comparison with that for thyroxine-binding globulin. 250 69

The hepatitis B virus (HBV) C gene directs the synthesis of two major gene products: HBV core antigen (HBcAg[p21c]), which forms the nucleocapsid, and HBV e antigen (HBeAg [p17e]), a secreted antigen that is produced by several processing events during its maturation. These proteins contain an amino acid sequence similar to the active-site residues of aspartic acid and retroviral proteases. On the basis of this sequence similarity, which is highly conserved among mammalian hepadnaviruses, a model has been put forward according to which processing to HBeAg is due to self-cleavage of p21c involving the proteaselike sequence. Using site-directed mutagenesis in conjunction with transient expression of HBV proteins in the human hepatoma cell line HepG2, we tested this hypothesis. Our results with HBV mutants in which one or two of the conserved amino acids have been replaced by others suggest strongly that processing to HBeAg does not depend on the presence of an intact proteaselike sequence in the core protein. Attempts to detect an influence of this sequence on the processing of HBV P gene products into enzymatically active viral polymerase also gave no conclusive evidence for the existence of an HBV protease. Mutations replacing the putatively essential aspartic acid showed little effect on polymerase activity. Additional substitution of the likewise conserved threonine residue by alanine, in contrast, almost abolished the activity of the polymerase. We conclude that an HBV protease, if it exists, is functionally different from aspartic acid and retroviral proteases.
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PMID:Proteaselike sequence in hepatitis B virus core antigen is not required for e antigen generation and may not be part of an aspartic acid-type protease. 265 1

Human hepatitis B virus (HBV) causes acute and chronic liver disease, which can result in tumor formation. An as yet unexplained phenomenon is that virus elimination usually correlates with the development of antibodies directed against the HBeAg, a secretory HBV core gene product which can be detected in the serum of infected patients. Expression of HBeAg in a human hepatoma cell line by using recombinant vaccinia viruses revealed that the HBeAg is not only secreted from HBeAg-producing cells but also incorporated into the outer cell membrane. No membrane-expressed core gene product could be detected when the cytoplasmic core protein (HBcAg) was expressed. Immune sera from patients who developed anti-HBe antibodies efficiently recognized the membrane-bound HBeAg, suggesting that surface-expressed HBeAg can serve as a target for an antibody-mediated elimination of HBV-infected cells.
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PMID:The secretory core protein of human hepatitis B virus is expressed on the cell surface. 268 56

A new hepatitis B virus (HBV) transcript of about 2.2 kilobases was identified in HBV DNA-transfected human hepatoma cells. The 5' terminus of this viral RNA appears to map at one or more of the precore initiation sites, contains a deletion of 1,223 bases corresponding to the last codon of the core gene to the middle of the surface antigen gene, and terminates at the 3' polyadenylation site used by the other known HBV RNAs. The junction region of the deleted sequences showed the conserved splice donor and acceptor GT-AG sequences. Moreover, when a mutant HBV DNA in which the splice acceptor site was changed from AG to CG was transfected into human hepatoma cells, no 2.2-kilobase RNA was detected, further suggesting that this RNA represents a spliced transcript. The core gene, although an amino acid shorter, still encoded a functional viral core protein in complementation experiments. Sequence analysis of the cDNA of the 2.2-kilobase RNA suggests that this transcript can potentially encode a new protein that comprises the reverse transcriptase domain of HBV. However, genetic analysis using a transient DNA transfection system suggests that the gene product(s) of this transcript is not essential for viral replication. The function of this transcript remains to be studied.
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PMID:Hepatitis B virus transcript produced by RNA splicing. 276 Sep 87

Several inner membrane proteins from rat liver mitochondria have been translated for the first time in rabbit reticulocyte lysates. These include the Rieske iron-sulfur protein, cytochrome c1 and core protein I of the cytochrome bc1 complex, the alpha and beta subunits of F1 ATPase, and subunit IV of cytochrome oxidase. All were translated from free polysomes as larger-molecular-mass precursors, and were processed to their mature forms by isolated liver mitochondria or by the isolated mitochondrial matrix fraction. In vitro processing, catalyzed by the isolated matrix fraction, is inhibited by rhodamine 6G. The latter is a fluorescent probe, which accumulates specifically in mitochondria of whole cells and which is used extensively to visualize mitochondrial morphology. The concentration of rhodamine 6G required for inhibition in vitro is similar to that of o-phenanthroline. Rhodamine 6G inhibits matrix-catalyzed processing of all precursors tested, indicating that the mechanism of inhibition is common for a variety of functionally unrelated precursors. The novel action of rhodamine 6G reported here can form the basis for its inhibition of precursor processing in intact hepatoma cells [Kolarov, J. & Nelson, B.D. (1984) Eur. J. Biochem. 144, 387-392].
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PMID:Rhodamine 6G inhibits the matrix-catalyzed processing of precursors of rat-liver mitochondrial proteins. 286 95

We have chemically synthesized a DNA duplex of 560 nucleotides that codes for the hepatitis B virus (HBV) core protein. The synthetic gene contains 27 unique internal restriction sites. Thereby, it can easily be mutagenized by replacement of rather short restriction fragments. A number of restriction recognition sequences are in common between the synthetic and the authentic gene, thus allowing for the transfer of synthetic segments into the cloned viral genome. Several unexpected mutations in the synthetic gene were readily corrected utilizing the multiple unique restriction sites. In Escherichia coli, the expression level of the synthetic gene product amounts to about 4% of the total soluble protein. It forms particles closely resembling native HBV cores. After transfer of the synthetic gene into the viral genome, transient expression in a hepatoma cell line yields proteins indistinguishable from the native gene products. The synthetic gene thus provides a useful tool for studies on the structure and function of the isolated HBV core protein as well as the gene and its various products in the viral life-cycle.
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PMID:Total chemical synthesis of a gene for hepatitis B virus core protein and its functional characterization. 290 97

Since both the liver and lung are derived from the endoderm, common antigens may appear on both tissues during malignant transformation. In an attempt to delineate cell surface alterations associated with the neoplastic transformation of these tissues, we have produced a library of monoclonal antibodies against a human hepatoma cell line termed FOCUS. One of these monoclonal antibodies, designated AF-10, recognized an antigen preferentially expressed on human lung adenocarcinoma cells, both in vitro and in vivo. This antigen has been characterized using Western immunoblot analysis and immunoprecipitation from surface-iodinated or metabolically labeled cells. The mature antigen is a cell surface glycoprotein with a core polypeptide with a molecular weight of 75,000 bearing N-glycosylation units. This protein migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an apparent molecular weight of 100,000-115,000 in reducing conditions and Mr 115,000-130,000 in nonreducing conditions. The epitope recognized by monoclonal antibody AF-10 is borne by the core protein. This antigen is shed from the cell surface and was identified in the culture supernatant from lung adenocarcinoma cell lines. Studies of the biodistribution of the AF-10 antigen showed that it was also expressed at low levels in normal human small intestine and kidney. The AF-10 monoclonal antibody may be useful for the study of the antigen expression between normal lung and the transformed phenotype.
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PMID:Characterization of a malignant phenotype-associated cell surface glycoprotein common to various human tumor cells and preferentially expressed on adenocarcinoma of the lung. 292 92

Primary hepatocellular carcinoma cells (PLC/342) propagated in nude mice produce hepatitis B surface antigen of subtype adr, as well as core particles containing viral DNA and DNA polymerase. Free and integrated forms of hepatitis B virus (HBV) DNA in the tumor were isolated by molecular cloning, and their nucleotide sequences were determined. Both of the two representative clones of free HBV DNA had the same genomic length (3,158 base pairs) and had two stop codons as well as two deletions in the envelope gene. None of the seven distinct clones of integrated HBV DNA possessed the entire viral genome. The integrated clone sequences had deletions and rearrangements, and only two clones possessed the envelope gene including the promoter and enhancer sequences. The C gene, which codes for core protein, was preserved in the two free clones and one of the integrated clones. The P gene, which codes for DNA polymerase, had deletions at two positions of 21 and 36 base pairs in both free clones, but was carried in toto by one of the integrated clones. The nucleotide sequences of the S genes of two free and four integrated clones, as well as their two inverted repeats, were compared. All of the eight sequences of the S gene possessed two nucleotide substitutions in common that were not displayed by any of the reported HBV genomes. The sequences differed from one another by only 1.2%. They differed, however, from 11 reported HBV genomes of subtype adr by 2.4%, from an ayr genome by 1.9%, from 2 adw genomes by 6.9%, and from 2 ayw genomes by 5.9%. These results indicate that all free and integrated HBV DNA species in the PLC/342 tumor cell evolved from a common progenitor. The free HBV DNA underwent nucleotide substitutions during several integration events, resulting in integrated HBV DNA copies that were similar in sequence but distinct from the reported HBV genomes.
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PMID:Free and integrated forms of hepatitis B virus DNA in human hepatocellular carcinoma cells (PLC/342) propagated in nude mice. 366 52

Analysis of the serum of duck hepatitis B virus (DHBV)-infected ducks has revealed the presence of C-terminally truncated viral core proteins (e antigens). These proteins are glycosylated and therefore were not released from infected cells by lysis but rather by active secretion, indicating that the DHBV core protein can be synthesized alternatively as a cytoplasmic or a secretory protein. Transient expression of cloned wild-type DHBV DNA and of a specifically designed viral mutant in a human hepatoma cell line (Hep-G2) showed that the DHBV core gene promoter is active in differentiated human liver cells and that synthesis and secretion of the processed core proteins are dependent on the expression of the pre-C region, a small open reading frame which precedes the core gene. In addition, these experiments showed that the mechanism of core protein processing and secretion is conserved between DHBV and the human hepatitis B virus and therefore might be important for the hepatitis B virus life cycle in general. In spite of this, intrahepatic injection of the pre-C mutant into uninfected ducks resulted in viremia without concomitant e-antigen synthesis, indicating that virus formation is independent of pre-C expression.
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PMID:The duck hepatitis B virus pre-C region encodes a signal sequence which is essential for synthesis and secretion of processed core proteins but not for virus formation. 368 59

Previous studies have shown that D-xylose partially overcomes the puromycin inhibition of chondroitin sulfate synthesis in cultured chick embryo chondrocytes. Likewise, D-xylose stimulates chondroitin sulfate synthesis by limb bud mesenchyme cells previously treated with BrdU or limb bud cartilage cells treated with puromycin. The studies reported here show that p-nitrophenyl-beta-D-xylopyranoside and 4-methyl-umbelliferyl-beta-D-xylopyranoside cause a much greater stimulation than does D-xylose and are active at much lower concentrations. In contrast to D-xylose, the xylosides strikingly stimulate chondroitin sulfate synthesis in predifferentiated mesenchyme cells. The xylosides stimulate synthesis of chondroitin sulfate by rat glial cell tumor cells (RC-6), a mouse neuroblastoma (C1300, NB41A), and two strains of cultured rat hepatoma cells (HTC, H(4)). These results indicate that certain types of nonconnective tissue cells contain the enzymic machinery for synthesis of chondroitin sulfate which is normally not utilized because of limited synthesis of core protein and/or xylosyltransferase. The beta-xylosides may be used as a probe of the capacity of various cell types to synthesize sulfated glycosaminoglycans.
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PMID:Stimulation of synthesis of free chondroitin sulfate chains by beta-D-xylosides in cultured cells. 437 4


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