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

Some peculiarities of mRNA translation of ceruloplasmin (CP) from rat liver were investigated, using three cell-free protein biosynthesis systems (wheat embryo extracts, rabbit reticulocyte lysates and Zajdela ascite hepatoma extracts). It was shown that reticulocyte lysates and tumour cell extracts synthesize full-size CP mRNA translation products, whose molecular mass is close to that of mature CP molecules, i. e., 122-132 kD. Wheat embryo extracts synthesize the NH2-terminal fragment of the CP molecule (Mr = 84 kD). Addition of liver membrane fractions to wheat embryo extracts translating CP mRNA results in the reconstitution of proteolytic steps of CP maturation.
 ...
PMID:[Comparative study of ceruloplasmin biosynthesis in various cell-free systems]. 381 51

The alpha-chain of the fourth component of complement (C4) contains tyrosine sulfate (Karp, D.R. (1983) J. Biol. Chem. 258, 12745-12748). Here we have determined the site and stoichiometry of sulfation of C4 secreted by the human hepatoma-derived cell line Hep G2. C4 was labeled with [35S]sulfate and isolated from culture medium by immunoprecipitation. C4 digested with trypsin and chymotrypsin and analyzed by reverse-phase high-performance liquid chromatography contained a single sulfate-labeled peptide. Digestion of C4 with trypsin alone yielded two major sulfate-labeled peptides, suggesting that there may be some sequence variability in C4 near the site of sulfation. Sequential Edman degradation of tryptic peptides labeled with [3H]tyrosine and [35S]sulfate detected tyrosine residues at positions 5, 13, 16, and 18. Chymotrypsin cleaved 5 residues off the NH2-terminal end of tryptic peptides, yielding a peptide with tyrosine at positions 8, 11, and 13. Comparison of the position of tyrosine residues with the reported sequence of C4 identified the sites of sulfation as tyrosine residues at positions 738, 741, and 743 in the alpha-chain of C4. All 3 of these tyrosine residues appeared to be sulfated. When sulfation of C4 was partially inhibited by addition of catechol to culture medium, three different forms of the peptide were resolved by high-performance liquid chromatography, consistent with peptides containing 1, 2, or 3 sulfates. Comparison of the quantities of tyrosine and tyrosine sulfate in C4 which had been labeled with [3H]tyrosine and digested with Pronase also indicated that C4 contained an average of 2-3 residues of tyrosine sulfate/molecule. These results suggest that the biologically active form of the protein is sulfated.
 ...
PMID:Identification of the site of sulfation of the fourth component of human complement. 394 9

The native and one of the modified forms of tyrosine aminotransferase were purified from rat liver and characterized. Several hydrodynamic properties of the native enzyme are: Stokes radius, 46 A; subunit isoelectric point, 5.6; sedimentation coefficient, 5.6 S, frictional ratio, 1.44; diffusion coefficient, 4.65 X 10(-7) cm2 s-1; extinction coefficient of a 1% solution (w:v) at 280 nm, 10.5 cm-1. The molecular weight of the dimeric protein is 110,500 as calculated from the Stokes radius and sedimentation coefficient. The subunit of the modified form is of lower molecular weight than the subunit of the native enzyme and has a pI of about 5.9. During isoelectric focusing, both forms of the enzyme separate into two components. The more acidic component that is resolved from the native enzyme is phosphorylated, but the other component is not. The amino acid composition of native tyrosine aminotransferase differs from values reported for mixtures of the three forms of this enzyme. Neither the native nor the modified forms of the enzyme possess a free alpha-amino group as judged by dansylation, nor can they be digested with leucine aminopeptidase, implying that the NH2-terminus is blocked. The possibility that tyrosine aminotransferase is acetylated was examined by translating poly(A)+RNA from hepatoma cells in a cell-free translational system in the presence and absence of inhibitors of protein acetylation. [35S]Tyrosine aminotransferase synthesized in the presence of the inhibitors has a more basic isoelectric point than the native enzyme as determined by isoelectric focusing, suggesting that the enzyme is acetylated either at the NH2-terminal or the epsilon-amino group of an internal lysine. When digested by either of two lysosomal proteases, tyrosine aminotransferase is cleaved to a smaller size. These data show that tyrosine aminotransferase is susceptible to several post-translational modifications.
 ...
PMID:Physical properties, limited proteolysis, and acetylation of tyrosine aminotransferase from rat liver. 611 52

The effects of folinic acid on a toxic pulse exposure of cultured hepatoma cells to methotrexate (4-amino-10-methylpteroylglutamic acid) is reported. Inclusion of folinic acid (5-formyl-5,6,7,8-tetrahydropteroylglutamic acid) (10 micro M) with the 2-hr pulse of methotrexate (10 micro M) nearly completely prevents the uptake and gamma-glutamylation of methotrexate and prevents toxicity. Addition of folinic acid after methotrexate results in a partial rescue that is time and concentration dependent. Restoration of cell growth in the presence of increasing amounts of folinic acid is accompanied by a concentration-dependent elevation in tritium release from [5-3H]deoxyuridine. In the absence of folinic acid, the release of tritium from [5-3H]deoxyuridine remains inhibited for three days after exposure to methotrexate, which can be related to the cellular formation and retention of methotrexate polyglutamates. Following the 2-hr pulse of methotrexate, the cellular pool consists of 70% polyglutamates of which the predominant species has three glutamate residues (4-NH2-10-CH3PteGlu3). When methotrexate is removed from medium, following the pulse, unmetabolized methotrexate rapidly leaves the cells, and 4-NH2-10-CH3PteGlu3 is converted to methotrexate polyglutamates containing four to six glutamate residues. Addition of folinic acid after the methotrexate pulse prevents the conversion of 4-NH2-10-CH3PteGlu3 to the higher-chain-length derivatives and causes a reduction in the total methotrexate cell pools over the next 48 hr. These results suggest that the effects of folinic acid on methotrexate polyglutamates may play a role in the rescue of cells containing these derivatives.
 ...
PMID:Effects of folinic acid on hepatoma cells containing methotrexate polyglutamates. 618 49

A protein kinase activity with high specificity for histone H1 was isolated from mouse plasmacytoma, Morris hepatoma and normal mouse liver and compared by ion exchange chromatography after DEAE-cellulose, hydroxylapatite and Sephadex G-200 chromatography. This cAMP-independent histone H1 kinase is not affected by the heat-stable cAMP-dependent protein kinase inhibitor. It has the following particular properties: it prefers GTP to ATP as substrate and was found to be present with a great activity only in neoplastic tissues. No phosphatase activity was detected in the partially purified histone H1 kinase fraction from normal and neoplastic cells. These results suggest either an increase amount of histone H1 kinase and/or of its activator in neoplastic cells, or the presence of a strong inhibitor in normal cells. This histone H1 kinase appears to be analogous to the chromatin bound kinase which phosphorylates histone H1 at the NH2 and COOH terminal regions. We might suggest an implication of this kinase in the regulation of cell division.
 ...
PMID:Microsomal cAMP-independent histone H1 kinase activity in plasmacytoma, Morris hepatoma and normal liver. 627 72

The phosphorylation of electrophoretically homogeneous preparations of the five major subcomponents of that thymus H1 histone by growth-associated histone kinase isolated from Ehrlich ascites tumor or Novikoff hepatoma cell chromatin results in the introduction of three to six phosphates/molecule into different subcomponents. Fully phosphorylated preparations of subcomponents 1 through 4 consist of H1 molecules containing a uniform number of phosphate groups, and run as single bands in long acid-urea gels. Fully phosphorylated preparations of subcomponent 5 consist of a mixture of molecules containing five and six phosphate groups. Phosphorylation of subcomponents 2, 4, and 5 occurs in both the NH2- and carboxyl-terminal regions of the molecules. Phosphorylation of subcomponents 1 and 3 occurs only in the carboxyl-terminal region. The central globular region of the histones is not phosphorylated. The major sites of phosphorylation in rat H1 histone subcomponents are similar to, but not entirely identical with, the major sites of phosphorylation previously characterized in total calf thymus H1, as determined by comparison of phosphopeptide maps. Highly phosphorylated rat H1 molecules, similar in phosphate content to those found in mitotic cells, have distinct chromatographic properties, compared to lightly phosphorylated molecules of the type found in interphase cells. This change in chromatographic properties appears to depend on the number of phosphate groups present in the histone rather than on the presence of phosphate in any specific sites.
 ...
PMID:Characterization of highly phosphorylated subcomponents of rat thymus H1 histone. 629 83

The primary translation product of human intestinal apolipoprotein A-I mRNA was isolated from wheat germ and ascites cell-free translation systems. Comparison of its NH2-terminal sequence with that of plasma high density lipoprotein-associated A-I showed that it is initially synthesized as a preproprotein. Like rat preproapolipoprotein A-I, it contains an 18-amino acid prepeptide and a 6-amino acid propeptide. The highly unusual COOH-terminal Gln-Gln dipeptide present in the rat pro-segment is also represented at the same position in the human sequence. The functional division of the 24-amino acid NH2-terminal extention into pro- and presegments was verified by finding that the stable intracellular form of A-I in a human hepatoma cell line was the proprotein. Edman degradation of radiolabeled intracellular and extracellular A-I indicated that this apolipoprotein was secreted without proteolytic cleavage of its hexapeptide prosegment. Therefore, it appears that apolipoprotein A-I undergoes an additional proteolytic processing step before it is fully integrated into plasma high density lipoprotein. Two-dimensional gel electrophoresis of purified proapolipoprotein A-I isolated from the hepatocyte cell culture media indicated that it corresponds to isoforms 2 and 3, the basic A-I isoproteins which are the precursors of plasma A-I and the predominant plasma A-I isoforms found in patients with Tangier's disease (Zannis, V. I., Lees, A. M., Lees, R. S., and Breslow, J. L. (1982) J. Biol. Chem., 257, 4978-4986). Therefore this pathologic state probably arises from a defect in the conversion of proapolipoprotein A-I to apolipoprotein A-I.
 ...
PMID:Proteolytic processing of human preproapolipoprotein A-I. A proposed defect in the conversion of pro A-I to A-I in Tangier's disease. 630 70

Immunoprecipitates of human C4 from EDTA-plasma were incubated with [14C]methylamine and analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and fluorography. In addition to finding label in the alpha-chains of the secreted (C4s) and predominant plasma (C4p) forms of C4, two additional molecules with apparent molecular weights of approximately 168,000 (p168) and approximately 125,000 (p125) covalently incorporated methylamine, indicating the presence of an internal thioester bond. These two molecules were present at a concentration of approximately 5% of total plasma C4 and were not immunoprecipitated by antisera to C3 or alpha 2-macroglobulin. A human hepatoma-derived cell line (HepG2), in addition to synthesizing C4s and small quantities of the polypeptide precursor of C4 (pro-C4), was found to secrete p168 and p125 at concentrations of 14 +/- 4.8 and 21 +/- 9.2% (mean +/- SD), respectively, of total secreted C4. These molecules were not found intracellularly. Both molecules were present on reduced, but not nonreduced, SDS-polyacrylamide gels. Chido (C4B) and Rodgers' (C4A) alloantisera precipitated the C4A and C4B variants of pro-C4, p168, p125, and C4s. Both tryptic and Staphylococcus aureus V8 protease peptide analyses showed homology between p168 and the beta- and alpha-chains and between p125 and the alpha- and gamma-chains. Partial NH2-terminal sequencing revealed that the beta-chain was NH2-terminal in p168 and that the alpha-chain was NH2-terminal in p125. Taken together, these data indicate that p168 and p125 represent uncleaved beta-alpha- and alpha-gamma-fragments of pro-C4, respectively. Thus, in most individuals, plasma C4 consists of five structurally distinct molecules, the single polypeptide precursor (pro-C4), the three-subunit secreted (C4s) and predominant plasma (C4p) forms of C4, and two incompletely processed two-subunit molecules with uncleaved beta-alpha- (p168) or uncleaved alpha-gamma (p125)-subunits. In addition, all five molecules are observed for both C4A (Rodgers) and C4B (Chido) structural genes.
 ...
PMID:Identification and structural characterization of two incompletely processed forms of the fourth component of human complement. 631 66

The primary translation product of human apolipoprotein A-II was purified from wheat germ and ascites cell-free lysates programmed with RNA isolated from either a hepatocellular carcinoma cell line (HepG2) or intestinal epithelium. A-II mRNA represents 0.2% of the translatable RNA in these hepatocytes and in jejunal epithelium. Plasma high density lipoprotein-associated A-II is a 77-amino acid polypeptide. The primary translation product is 100 amino acids long and contains a 23-amino acid NH2-terminal extension. Cotranslational cleavage of the cell-free product indicated that this NH2-terminal sequence consists of an 18-amino acid long signal peptide, Met-Lys-Leu-Leu-Ala-Ala-X-Val-Leu-Leu-Leu-X-X-Cys-X-Leu-X-X-, and a 5-amino acid long propeptide, Ala-Leu-Val-Arg-Arg. This functional division was confirmed by sequencing the stable intracellular form of apolipoprotein A-II isolated from HepG2 cells. Approximately 45% of the proapo-A-II is cleaved to the mature form during export from HepG2 cells. The COOH-terminal dipeptide conforms to the rule that prosegments are cleaved after paired basic residues. We have previously shown (Gordon, J. I., Sims, H. F., Lentz, S. R., Edelstein, C., Scanu, A. M., and Strauss, A. W. (1983) J. Biol. Chem. 258, 4037-4044) that proapolipoprotein A-I is not cleaved during export from these cells and contains a prosegment with a COOH-terminal Gln-Gln dipeptide. Therefore, proteolytic processing of the two principal high density lipoprotein-associated apolipoproteins proceeds along different pathways.
 ...
PMID:Biosynthesis of human preproapolipoprotein A-II. 631 18

Gelsolin is an actin-fragmenting cytoplasmic protein. A functionally similar protein has also been identified in plasma. We have compared the structure of the cytoplasmic and plasma forms of gelsolin and examined their biosynthetic relationships. Plasma gelsolin is larger than cytoplasmic gelsolin (Mr 93,000 versus 90,000, respectively) and is more positively charged. Partial amino acid sequencing analyses show that the two gelsolins share a common 29 amino acid sequence which lies at the NH2-terminal end of cytoplasmic gelsolin and spans residues 26-55 of plasma gelsolin. Compared with cytoplasmic gelsolin, plasma gelsolin contains an additional peptide of 25 amino acids at its NH2 terminus. The human hepatoma-derived cell line, HepG2, synthesizes both the 90-kDa and the 93-kDa gelsolins but secretes only the 93-kDa form. Pulse-chase experiments demonstrate that the rate of disappearance of the 93-kDa gelsolin from the cells corresponds with the rate of appearance of the 93-kDa gelsolin in the medium, whereas the rate of disappearance of the 90-kDa gelsolin is independent of and slower than that of the secreted plasma protein. We conclude that cytoplasmic and plasma gelsolins are structurally similar but not identical, that after synthesis these proteins are processed independently, and that the fate of each is distinct.
 ...
PMID:Structure and biosynthesis of cytoplasmic and secreted variants of gelsolin. 632 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>