Synthesis, transport, and processing of apolipoproteins of high density lipoproteins.

Cell biology methods have greatly influenced the elucidation of the biosynthetic pathways of apolipoproteins. In vitro and tissue culture systems allow the study, to a large extent, of the process of synthesis, intracellular processing, secretion, and extracellular processing of the major high density lipoprotein apoproteins apoA-I and A-II and also of a minor component, apoA-IV. Whereas the latter apoprotein is equipped only with a signal sequence, the primary translation products of apoA-I and apoA-II carry N-terminal extensions of preprosequence of 24 amino acids for apoA-I and 23 amino acid residues for apoA-II. The pro-form of apoA-I characterized by a hexapeptide extension is completely stable intracellularly and is secreted as such. The pro-form is further processed by a serum protease specific for an unusual -Gln-Gln-Asp-Glu-sequence site. Pro-apoA-II, a pentapeptide sequence, is partially processed intracellularly to its mature form and secreted together with the residual pro-form. The cleavage site of pro-apoA-II is characterized by two basic amino acid residues Arg-Arg, present also in other known pro-proteins. The biological function of the N-terminal pro-sequences and details of their final processing by the serum protease(s) have yet to be established.

[1]  J. Gordon,et al.  Biosynthesis of human preapolipoprotein A-IV. , 1984, The Journal of biological chemistry.

[2]  G. Blobel,et al.  Intracellular protein topogenesis. , 1980, Progress in clinical and biological research.

[3]  H. Brewer,et al.  Nucleotide sequence and the encoded amino acids of human apolipoprotein A-I mRNA. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[4]  J. Gordon,et al.  Biosynthesis of human preproapolipoprotein A-II. , 1983, The Journal of biological chemistry.

[5]  W. Stoffel,et al.  A serum proteinase converts proapolipoprotein AI secreted by rat hepatocytes to the mature apolipoprotein. , 1983, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[6]  J. G. Lill,et al.  In vitro conversion of proapoprotein A-I to apoprotein A-I. Partial characterization of an extracellular enzyme activity. , 1983, The Journal of biological chemistry.

[7]  J. Breslow,et al.  Isolation and characterization of the human apolipoprotein A-I gene. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[8]  H. Brewer,et al.  Human plasma proapoA-I: isolation and amino-terminal sequence. , 1983, Biochemical and biophysical research communications.

[9]  L. Chan,et al.  Nucleotide sequence of cloned cDNA of human apolipoprotein A-I. , 1983, Nucleic Acids Research.

[10]  A. Kornblihtt,et al.  Gene structure of human apolipoprotein A1. , 1983, Nucleic acids research.

[11]  J. Breslow,et al.  Intracellular and extracellular processing of human apolipoprotein A-I: secreted apolipoprotein A-I isoprotein 2 is a propeptide. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[12]  W. Stoffel,et al.  Serum apolipoprotein AI synthesis in rat hepatocytes and its secretion as proform. , 1983, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[13]  W. Stoffel,et al.  Cell-free translation of human liver apolipoprotein AI and AII mRNA. Processing of primary translation products. , 1983, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[14]  Peter Walter,et al.  Signal recognition particle contains a 7S RNA essential for protein translocation across the endoplasmic reticulum , 1982, Nature.

[15]  J. Breslow,et al.  Hepatic apo-A-I and apo-E and intestinal apo-A-I are synthesized in precursor isoprotein forms by organ cultures of human fetal tissues. , 1982, The Journal of biological chemistry.

[16]  J. Breslow,et al.  Characterization of the major apolipoproteins secreted by two human hepatoma cell lines. , 1981, Biochemistry.

[17]  G. Blobel,et al.  Synthesis in vitro and translocation of apolipoprotein AI across microsomal vesicles. , 1981, European journal of biochemistry.

[18]  W. A. Bradley,et al.  Characterization, cell-free synthesis, and processing of apolipoprotein A-I of rat high-density lipoproteins. , 1981, Biochemistry.

[19]  A. Katz,et al.  Isoproteins of human apolipoprotein A-I demonstrated in plasma and intestinal organ culture. , 1980, The Journal of biological chemistry.

[20]  M. J. Chapman.  Animal lipoproteins: chemistry, structure, and comparative aspects. , 1980, Journal of lipid research.

[21]  C C Howe,et al.  Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. , 1980, Science.

[22]  D. Steiner,et al.  PROCESSING MECHANISMS IN THE BIOSYNTHESIS OF PROTEINS * , 1980, Annals of the New York Academy of Sciences.

[23]  A. Tall,et al.  Human intestinal lipoproteins. Studies in chyluric subjects. , 1979, The Journal of clinical investigation.

[24]  R. Mahley,et al.  Isolation and characterization of an apoprotein from the d<1.006 lipoproteins of human and canine lymph homologous with the rat A-IV apoprotein , 1978 .

[25]  G. Warren,et al.  Protein transfer across microsomal membranes reassembled from separated membrane components , 1978, Nature.

[26]  H. Brewer,et al.  The amino acid sequence of human APOA-I, an apolipoprotein isolated from high density lipoproteins. , 1978, Biochemical and biophysical research communications.

[27]  A. Tall,et al.  Rat intestine secretes discoid high density lipoprotein. , 1978, The Journal of clinical investigation.

[28]  R. Havel,et al.  Secretion of the arginine-rich and A-I apolipoproteins by the isolated perfused rat liver. , 1977, Journal of lipid research.

[29]  B. Dobberstein,et al.  Transfer of proteins across membranes. I. Presence of proteolytically processed and unprocessed nascent immunoglobulin light chains on membrane-bound ribosomes of murine myeloma , 1975, The Journal of cell biology.

[30]  K. Balzer,et al.  Isolierung intakter Leberparenchymzellen durch eine modifizierte enzymatische Methode , 1975 .