Role of lipid synthesis, chaperone proteins and proteasomes in the assembly and secretion of apoprotein B-containing lipoproteins from cultured liver cells.
1. Apolipoprotein B (apoB) is necessary for the assembly and secretion of both chylomicrons from the small intestine and very low-density lipoproteins (VLDL) from the liver. ApoB is also the major protein in low-density lipoproteins (LDL) and is the ligand for the LDL receptor. Studies in humans suggest that increased production of apoB-containing lipoproteins, particularly VLDL, is a common abnormality in dyslipidaemias. 2. Studies in primary and long-term cultures of hepatocytes and hepatoma cells indicate that a significant proportion of newly synthesized apoB is rapidly degraded and that this is the major mechanism for regulation of apoB secretion. The availability of newly synthesized lipids, particularly triglyceride and cholesteryl ester, appears to be a critical factor in targeting apoB for secretion rather than degradation. 3. ApoB is an atypical secretory protein in that cotranslational translocation across the endoplasmic reticulum membrane, a feature of all secretory proteins, seems to slow or stop in the absence of adequate lipid availability (or in the absence of microsomal triglyceride transfer protein), allowing for rapid degradation of apoB. 4. The degradation of apoB seems to be facilitated by the association of nascent apoB with the major cytosolic chaperone protein, heat shock protein 70. Additionally, degradation of nascent apoB appears to occur, to a large degree, via the proteasomal pathway for degradation of cytosolic proteins.
Ginsberg
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Department of Medicine, College of Physicians and Surgeons of Columbia University, New York 10032-3784, USA.
D001055:Apolipoproteins B / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex
D001055:Apolipoproteins B; D018840:HSP70 Heat-Shock Proteins; D008074:Lipoproteins; D018832:Molecular Chaperones; D009097:Multienzyme Complexes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex