The occurrence of nonglycosylated forms of N-glycoprotein upon proteasome inhibition does not confirm cytosolic deglycosylation.
The occurrence of nonglycosylated forms of N-glycoprotein upon proteasome inhibition does not confirm cytosolic deglycosylation.
复制标题
蛋白酶体抑制后 N-糖蛋白非糖基化形式的出现并不能证实胞质去糖基化。
DOI：
10.1002/1873-3468.13734
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Suzuki T.
中科院分区：
文献类型：
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作者：
Huang C;Suzuki T.
经历内质网相关降解(ERAD)的N-糖基化底物在胞浆中的蛋白酶体降解过程中，通常会被胞内肽：N-葡聚糖酶(N-Gly1)去糖化。因此，在蛋白酶体抑制剂处理后，这些蛋白质的非糖基化或脱糖形式的存在被广泛用作胞浆脱糖基化的证据。然而，在这项研究中，当用蛋白酶体抑制剂处理时，在缺乏胞浆去N-糖基化酶的小鼠细胞中，仍然观察到非糖基化的Rta∆m，一个模型ERAD底物。研究发现，Rta∆m通常是部分N-糖基化的，而非糖基化的形式会被胞浆中的蛋白酶体迅速降解。我们的结果表明，在用蛋白酶体抑制剂处理时，“非糖化的”ERAD底物的出现并不一定是胞浆去糖化的线索。
N‐Glycosylated substrates that undergo ER‐associated degradation (ERAD) are often deglycosylated by the cytosolic peptide:N‐glycanase (Ngly1) during their proteasomal degradation in the cytosol. Consequently, the presence of non‐ or deglycosylated forms of such proteins after treatment with proteasome inhibitors is widely used as evidence for cytosolic deglycosylation by Ngly1. However, in this study, the accumulation of nonglycosylated RTA∆m, a model ERAD substrate, was still observed in mouse cells lacking cytosolic de‐N‐glycosylating enzymes, when treated with proteasome inhibitors. It was found that RTA∆m is normally partiallyN‐glycosylated, while the nonglycosylated form is rapidly degraded by proteasomes in the cytosol. Our results suggest that the occurrence of ‘nonglycosylated’ ERAD substrates upon treatment with proteasome inhibitors is not necessarily a clue for cytosolic deglycosylation.