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)

Rat liver coated vesicle preparations were frequently found to contain small ovoid bodies, which resembled coated vesicles in morphology. We have purified these bodies to homogeneity using sucrose density gradients and preparative agarose gel electrophoresis. When negatively stained and viewed by electron microscopy, the purified structures display a very distinct and complex morphology, resembling the multiple arches which form cathedral vaults. They measure 35 X 65 nm and are therefore considerably larger than ribosomes. When subjected to SDS PAGE, these structures, which we refer to as vaults, appear to contain several minor and five major species: Mr 210,000, 192,000, 104,000, 54,000, and 37,000. One of these (Mr 104,000) greatly predominates, accounting for greater than 70% of the total Coomassie Brilliant Blue-staining protein. Another major species of Mr 37,000 has been identified as a species of small RNA of unusual base composition (adenosine 12.0%, guanosine 29.7%, uridine 30.9%, and 27.4% cytidine), which migrates as a single species in urea PAGE between the 5S and 5.8S ribosomal standards, containing approximately 140 bases. Although the RNA constitutes only 4.6% of the entire structure, the large size of the particle requires that each one contains approximately 9 molecules of this RNA. Antibodies prepared against the entire particle are largely specific for the major (Mr 104,000) polypeptide species. Although they do not directly react with the RNA constituent on Western blots, these antibodies immunoprecipitate a 32P-labeled RNA of identical size from metabolically-labeled rat hepatoma cells. Vaults are observed in partially purified fractions from human fibroblasts, murine 3T3 cells, glial cells, and rabbit alveolar macrophages. It therefore appears that these novel ribonucleoprotein structures are broadly distributed among different cell types. The function of vaults is at present unknown.
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PMID:Isolation and characterization of a novel ribonucleoprotein particle: large structures contain a single species of small RNA. 294 44

The mRNAs for the heavy and light subunits of the iron-storage protein ferritin occur in cells largely as inactive ribonucleoprotein particles, which are recruited for translation when iron enters the cell. Cytoplasmic extracts from rat tissues and hepatoma cells were shown by an electrophoretic separation procedure to form RNA-protein complexes involving a highly conserved sequence in the 5' untranslated region of both ferritin heavy- and light-subunit mRNAs. The pattern of complex formation was affected by pretreatment of rats or cells with iron. Crosslinking by UV irradiation showed that the complexes contained an 87-kDa protein interacting with the conserved sequence of the ferritin mRNA. We propose that intracellular iron levels regulate ferritin synthesis by causing changes in specific protein binding to the conserved sequence in the ferritin heavy- and light-subunit mRNAs.
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PMID:Cytoplasmic protein binds in vitro to a highly conserved sequence in the 5' untranslated region of ferritin heavy- and light-subunit mRNAs. 312 26

The association of nucleolar phosphoprotein C23 with preribosomal ribonucleoprotein (RNP) particles was examined in Novikoff hepatoma nucleoli. RNA was labeled with [3H]uridine for various times in cell suspensions, and RNP particles were extracted from isolated nucleoli and fractionated by sucrose gradient ultracentrifugation. The majority of protein C23 cosedimented with fractions containing rapidly labeled RNA (RL fraction). To determine whether there was a direct association of RNA with protein C23, the RL fraction was exposed to ultraviolet (UV) light (254 nm) for short periods of time. After 2 min of exposure there was a 50% decrease in C23 as measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analyses, with no significant further decrease at longer times. When UV-treated fractions were subjected to phenol/chloroform extractions, as much as 30% of the labeled RNA was found in the phenol (protein) layer, indicating that RNA became cross-linked to protein. Similarly, there was an increase in protein C23 extracted into the water layer after irradiation. By SDS-PAGE analyses the cross-linked species migrated more slowly than protein C23, appearing as a smear detected either by [3H]uridine radioactivity or by anti-C23 antibody. With anti-C23 antibodies, up to 25% of the labeled RNA was precipitated from the RL fraction. Dot-blot hybridizations, using cloned rDNA fragments as probes, indicated that the RNA in the RL fraction and the immunoprecipitated RNA contained sequences from 18S and 28S ribosomal RNA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Association of protein C23 with rapidly labeled nucleolar RNA. 379 May 20

To elucidate the possible role of nucleolar phosphoprotein B23 in ribosome synthesis, drugs which inhibit the processing of ribosomal RNA were employed. After treatment with actinomycin D, toyocamycin or high doses of alpha-amanitin, a uniform nucleoplasmic fluorescence was observed. Low doses of alpha-amanitin and the protein synthesis inhibitor puromycin and cycloheximide had no effect on protein B23 translocation. By ELISA immunoassay, there was a 60% decrease in the amount of protein B23 in the nucleoli of the actinomycin D-treated cells as compared with the control nucleoli. Conversely, the amount of protein B23 in the nucleoplasm (excluding nucleoli) was 3-fold higher in the actinomycin D-treated cells. Preribosomal ribonucleoprotein particles (pre-rRNPs) were extracted from isolated nucleoli of Novikoff hepatoma ascites cells and fractionated on sucrose density gradients. Protein B23 was found co-localized with the pre-rRNPs as determined by ELISA assays which agrees with previous studies. The proteins in these 80 S and 55 S pre-ribosomal ribonucleoprotein particles were fractionated by 10% gel electrophoresis. Immunoblots showed protein B23 was present in both pre-rRNPs.
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PMID:Translocation of nucleolar phosphoprotein B23 (37 kDa/pI 5.1) induced by selective inhibitors of ribosome synthesis. 390 10

U3 RNA, a capped small nuclear RNA found thus far only in the nucleolus, has been implicated in the processing and/or transport of preribosomal RNA [Busch, H., Reddy, R., Rothblum, L., & Choi, Y. C. (1982) Annu. Rev. Biochem. 51, 617-654]. Tris(hydroxymethyl)aminomethane (Tris) (10 mM, pH 7.0) extracts of Novikoff hepatoma nucleoli, which contained about 80% of total nucleolar U3 RNA, were analyzed by sucrose density gradient centrifugation. Approximately 65% of the U3 RNA was bound to greater than 60S preribosomal ribonucleoprotein (RNP) particles, and about 15% sedimented at less than 20 S. The association between the 65% of U3 RNA that was bound to the preribosomal RNP particles was stable up to 55 degrees C. About 10% of U3 RNA was base paired to preribosomal RNA after deproteinization at 22 degrees C. The base-paired fraction of U3 RNA was released from the preribosomal RNA by heating to 45 degrees C or treating with 4 M urea. These results show that of the total nucleolar U3 RNP, (a) about 55% is bound to preribosomal RNP particles primarily by protein interactions, (b) about 10% is base paired to preribosomal RNA, (c) approximately 15% sedimented slowly and consisted presumably of free U3 RNP particles, and (d) the remaining 20% of U3 RNP was not extractable using 10 mM Tris buffer. On the basis of the different association states of U3 RNP particles, a model is proposed for the binding and dissociation events which take place between U3 RNP and preribosomal RNP particles.
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PMID:Multiple states of U3 RNA in Novikoff hepatoma nucleoli. 621 Jan 4

Poly(adenylic acid)-containing rat liver polysomal messenger ribonucleoprotein particles (pmRNP) were isolated and found to contain protein kinase activity. The association of the enzyme(s) with the particles was confirmed by experiments showing that the protein kinase activity comigrated with the pmRNP on metrizamide gradients and bound to oligo-(dT)-cellulose columns only under conditions where the pmRNP bound. The following properties were determined for the pmRNP-associated kinase(s). Casein and phosvitin were preferred substrates over histone and protamine. The optimal MgCl2 and KCl concentrations were found to be 12.5 and 50 mM, respectively. MnCl2 and CaCl2 could not replace MgCl2 and were inhibitory at low concentrations. The optimum pH range was 7.7--9.0, and the enzyme activity was cAMP independent. A molecular weight of 55 000--60 000 was determined for the kinase(s) by sucrose gradient analysis. The enzyme(s) was capable of phosphorylating proteins endogenous to the pmRNP. Membrane-bound pmRNP contained much less kinase activity than free pmRNP while pmRNP from hepatoma 7777 contained an elevated level of the enzyme(s). The relationship between the protein kinase activity and one of the pmRNP proteins of molecular weight 66 000 is discussed.
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PMID:Characterization of protein kinase activity associated with rat liver polysomal messenger ribonucleoprotein particles. 625 May 53

In view of the increasing interest in low molecular weight ribonucleoprotein particles in exon-intron binding and cleavage reactions (Lerner, M. R., Boyle, J. A., Mount, S. M., Wolin, S. L., and Steitz, J. A. (1980) Nature 283, 220--224), the complementarity of the conserved regions to HnRNAs, or protein binding sites, or both, is of potential importance. U3A, U3B, and U3C are three RNA species localized to the nucleolus of Novikoff hepatoma cells. The nucleotide sequence of U3A RNA determined in this study was compared to that of U3B RNA (Reddy, R., Henning, D., and Busch, H. (1979) J. Biol. Chem. 254, 11097--11105). Both U3A and U3B RNAs contained 5' "caps" and were 216 nucleotides long. The nucleotide sequence 1 to 87 was identical in both U3A and U3B, but differences were found at 18 positions in the remainder of the sequence. Of these differences, 11 were single base replacements, two were dinucleotide replacement AU leads to GG at positions 93 to 94, UC leads to GG at positions 173 to 174, and one was a trinucleotide replacement, UCG leads to CUU at positions 179 to 181. Of the total 18 base replacements, 11 (61%) were purine leads to purine or pyrimidine leads to pyrimidine. Interestingly, two base insertions/deletions were found in each RNA when both RNA sequences were compared for maximum sequence similarity. These data establish that the heterogeneity of some low molecular weight nuclear and nucleolar RNA species resulted from a small number of mutations but much of the sequence was conserved.
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PMID:Substitutions, insertions, and deletions in two highly conserved U3 RNA species. 677 Dec 80

Anti-La antibodies are frequently found in patients with autoimmune diseases; the antigen was reported to be a 50,000-Da protein (Rinke, J., and Steitz, J. A. (1982) Cell 29, 149-159). Because this protein was associated with many nascent RNA polymerase III transcripts, it was suggested to be an RNA polymerase III transcription factor. The present study was designed to analyze 4.5 I ribonucleoprotein, an RNA polymerase III transcript which contains the La antigen. It was found that the 3'-end 20-30-nucleotide portion was the most protected portion of 4.5 I RNA when 4.5 I ribonucleoprotein was digested with T1 RNase. When U2 RNA (an RNA polymerase II transcript) and 4.5 I RNA were incubated with the S-100 fraction of Novikoff hepatoma cells, the 4.5 I RNA bound La antigen but the U2 RNA did not. When partial and complete T1 RNase digestion fragments of 4.5 I RNA were incubated with the S-100 fraction, the 3'-end fragments bound preferentially to the La antigen. However, the fragments of 4.5 I RNA bound less efficiently to La antigen than whole 4.5 I RNA. These results indicate that the 3'-end of 4.5 I RNA is the La antigen binding site in this molecule and suggest that the overall conformation of RNA aids in the binding of La antigen.
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PMID:Identification of a La protein binding site in a RNA polymerase III transcript (4.5 I RNA). 686 91

Antibodies were raised in chickens against heterogeneous nuclear RNA (hnRNA)-binding proteins from 30S ribonucleoprotein (RNP) complexes of mouse Taper hepatoma ascites cell nuclei. The antibody preparations were characterized for immunological specificity and purity by double-diffusion gels, binding to specific bands in SDS polyacrylamide gels, and crossed immunoelectrophoresis. Antibodies raised against either whole 30S RNP complexes or purified RNP core proteins had a strong selective affinity for the four 34,000- to 40,000-dalton polypeptides which comprise the major structural proteins of hnRNP. The intracellular distribution of 30S RNP antigens in mouse ascites cells was determined by indirect immunofluorescence microsacopy. In interphase cells immunofluorescent sites were restricted to the nucleus, and nucleoli were free of fluorescence. The chicken anti-mouse-RNP antibodies were also able to react with cells from many different vertebrate species, showing a similar nucleus-restricted localization of the reacting sites. The antibodies also bound chick 30S RNP-proteins and reacted with the nuclei of chick cells. An exception to this was the failure of the antibody to bind to adult chick erythrocytes, suggesting that these major hnRNA binding proteins may be found only in nuclei capable of RNA synthesis.
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PMID:Immunofluorescent localization of the proteins of nuclear ribonucleoprotein complexes. 699 85

Cationic liposomes are known to facilitate efficient transfection of animal cells with DNA and even some viruses. As reported here, we have been able to use such a commercially available formulation (Lipofectamine) and introduce human hepatitis delta virus (HDV) into lines of cultured cells and demonstrate replication of the HDV genome both by immunofluorescence and by Northern (RNA) analysis. As much as 10% of the human hepatoma cell line Huh7 was transfected with HDV. Also transfected were the baby hamster kidney cell line BHK-21 and the Morris rat hepatoma line 7777. Two initial applications of HDV transfection have been made. (i) The ribonucleoprotein structure of HDV was isolated from disrupted virions and demonstrated as being sufficient to transfect Huh7 cells. In contrast, naked HDV RNA was not sufficient. (ii) From a study of cells transfected with HDV particles, it was found that, even after as long as 7 weeks and the associated replication of the transfected cells, the HDV RNA genome was still replicating. Apparently, HDV, in the absence of helper virus and in the absence of virus assembly, can maintain persistent replication and expression of the HDV genome. Transfection was also achieved with woodchuck hepatitis virus introduced into Huh7 cells. In summary, this transfection procedure should be of use for the study of these and maybe other recalcitrant animal viruses.
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PMID:Introduction of hepatitis delta virus into animal cell lines via cationic liposomes. 803 21


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