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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >MISFOLDED MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I HEAVY CHAINS ARE TRANSLOCATED INTO THE CYTOPLASM AND DEGRADED BY THE PROTEASOME
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MISFOLDED MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I HEAVY CHAINS ARE TRANSLOCATED INTO THE CYTOPLASM AND DEGRADED BY THE PROTEASOME

机译：错位的主要组织相容性复杂的I类重链被转运到细胞浆中并被蛋白质组降解

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摘要

N-acetyl-L-leucyl-L-leucyl-L-norleucinal (LLnL), which reversibly inhibits the proteasome in addition to other proteases, and a more specific irreversible inhibitor of the proteasome, lactacystin, were found to cause the accumulation of major histocompatibility complex (MHC) class I heavy chains in the cytosol of the beta(2)-microglobulin-deficient cell line Daudi and the TAP-deficient cell line .174. These cell lines, which are severely impaired in their ability to fold MHC class I heavy chain, showed an accumulation of soluble class I heavy chains at different rates over a period of hours in the presence of LLnL, The accumulation of soluble class I heavy chains in the presence of either LLnL or lactacystin was easily revealed in Daudi and .174 but almost undetectable in a Daudi transfectant expressing beta(2)-microglobulin and in 45.1, the wild-type parent of .174, The soluble class I heavy chain was also found to be devoid of its N-linked glycan and to be located in the cytosol, When the gene for ICP47, a herpes simplex virus protein that blocks the translocation of peptides into the endoplasmic reticulum, was transfected into 45.1, a similar accumulation of soluble MHC class I heavy chain was detectable, These data suggest that in cells where the MHC class I molecule is unable to assemble properly, the misfolded heavy chain is removed from the endoplasmic reticulum to the cytosol, deglycosylated, and degraded by the proteasome. [References: 43]
机译：N-乙酰基-L-亮氨酰-L-亮氨酰-L-净亮氨酸（LLnL），除其他蛋白酶外，它还​​可逆地抑制蛋白酶体，并且发现蛋白酶体的一种更特异性的不可逆抑制剂乳杆菌素引起了主要蛋白质的积累β（2）-微球蛋白缺陷细胞系Daudi和TAP缺陷细胞系.174的细胞质中的组织相容性复合物（MHC）I类重链。这些细胞系折叠MHC I类重链的能力受到严重损害，在存在LLnL的情况下，在几个小时内，可溶性I类重链以不同的速率积累，可溶性I类重链的积累在Daudi和.174中很容易发现存在LLnL或乳酸的情况，但是在表达β（2）-微球蛋白的Daudi转染子中几乎检测不到，而在45.1中，.174的野生型亲本，可溶性I类重链当发现ICP47的基因（一种阻止肽向内质网转运的单纯疱疹病毒蛋白）被转染到45.1时，也发现它不含N-连接的聚糖并且位于胞质溶胶中。可溶性MHC I类重链是可检测的，这些数据表明，在MHC I类分子无法正确组装的细胞中，错误折叠的重链从内质网转移到胞质1，被糖基糖基化并降解。 [参考：43]

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