Tunicamycin induces ubiquitination and degradation of apolipoprotein B in HepG2 cells
Tunicamycin induces ubiquitination and degradation of apolipoprotein B in HepG2 cells
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DOI：
10.1042/0264-6021:3530493
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发表时间：
2001-02-01
影响因子：
4.1
通讯作者：
Chan, L
中科院分区：
文献类型：
--
作者：
Liao, W;Chan, L
载脂蛋白（apo）B-100是致动脉粥样硬化血浆脂蛋白的重要组成部分。以往的研究表明，apoB-100的生产主要是由细胞内降解的共翻译和翻译后水平，蛋白酶体介导的和非蛋白酶体介导的途径参与了这一过程。ApoB-100是糖蛋白。本研究旨在解决衣霉素抑制N-连接糖基化是否会干扰apoB-100的产生的问题。我们证明了用衣霉素处理HepG 2细胞通过增强蛋白质的共翻译降解来降低apoB-100的净产量。由于lactacystin仅部分逆转了衣霉素对apoB生物合成的影响，衣霉素似乎还通过一个或多个非蛋白酶体途径诱导apoB在HepG 2细胞中的共翻译降解。4倍，新合成的apoB-100分泌并掺入新生脂蛋白颗粒的比例不受衣霉素的影响。因此，衣霉素介导的N-连接糖基化抑制干扰了由蛋白酶体和非蛋白酶体途径介导的apoB-100的产生。
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 posttranslational 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.