Tunicamycin induces ubiquitination and degradation of apolipoprotein B in HepG2 cells.
Apolipoprotein (apo) B-100 is an essential component of atherogenic plasma lipoproteins. Previous studies have demonstrated that the production of apoB-100 is regulated largely by intracellular degradation at both the co-translational and post-translational levels and that proteasome-mediated and non-proteasome-mediated pathways are involved in this process. ApoB-100 is a glycoprotein. The present study was undertaken to address the question of whether the inhibition of N-linked glycosylation with tunicamycin would interfere with apoB-100 production. We demonstrated that the treatment of HepG2 cells with tunicamycin decreased the net production of apoB-100 by enhancing co-translational degradation of the protein. This effect of tunicamycin was partly prevented by lactacystin, a specific proteasome inhibitor. Because lactacystin only partly reversed the effects of tunicamycin on apoB biogenesis, tunicamycin seemed also to induce apoB co-translational degradation in HepG2 cells by one or more non-proteasomal pathways. Furthermore, tunicamycin increased apoB ubiquitination approx. 4-fold. The proportion of the newly synthesized apoB-100 that was secreted and incorporated into the nascent lipoprotein particles was unaffected by tunicamycin. Thus the tunicamycin-mediated inhibition of N-linked glycosylation interferes with the production of apoB-100 that is mediated by both proteasomal and non-proteasomal pathways.
Liao
W
W
Department of Molecular and Cellular Biology, 1 Baylor Plaza, Baylor College of Medicine, Houston, TX 77030-3498, USA.
Chan
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L
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D009097:Multienzyme Complexes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D014415:Tunicamycin / Q000494:pharmacology*; D014452:Ubiquitins / Q000378:metabolism*
D001055:Apolipoproteins B; D009097:Multienzyme Complexes; D014452:Ubiquitins; D014415:Tunicamycin; C067713:lactacystin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine