A ROLE FOR THE UBIQUITIN-DEPENDENT PROTEOLYTIC PATHWAY IN MHC CLASS I-RESTRICTED ANTIGEN PRESENTATION
A ROLE FOR THE UBIQUITIN-DEPENDENT PROTEOLYTIC PATHWAY IN MHC CLASS I-RESTRICTED ANTIGEN PRESENTATION
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DOI：
10.1038/363552a0
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发表时间：
1993-06-10
期刊：
影响因子：
64.8
通讯作者：
ROCK, KL
中科院分区：
文献类型：
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作者：
MICHALEK, MT;GRANT, EP;ROCK, KL
大多数细胞蛋白质的降解始于它们与泛素1,2 的共价结合。这会标记蛋白质，以便通过包含称为蛋白酶体的 (20S) 降解颗粒的 (26S) 蛋白水解复合物快速水解为寡肽3,4。细胞质中的一些系统还从内源合成的细胞和病毒蛋白5-10 中产生抗原肽。这些肽与内质网中新合成的 I 类主要组织相容性复合物分子结合，然后肽/I 类复合物被转运到细胞表面，呈递给细胞毒性 T 细胞11,12。这些肽是如何产生的尚不清楚，尽管促进病毒蛋白泛素依赖性降解的修饰增强了其 I13 类的呈递，并且间接证据表明与蛋白酶体非常相似甚至可能相同的蛋白水解颗粒的作用4,12,14,15。使用泛素缀合中表现出温度敏感缺陷的细胞，我们在此报告，非允许的温度抑制了引入细胞质中的卵清蛋白的 I 类限制性呈递，但不影响由小基因合成的卵清蛋白肽的呈递。这些结果表明抗原肽生产中存在泛素依赖性蛋白水解途径。
THE degradation of most cellular proteins starts with their covalent conjugation with ubiquitin1,2. This labels the proteins for rapid hydrolysis to oligopeptides by a (26S) proteolytic complex containing a (20S) degradative particle called the proteasome3,4. Some system in the cytosol also generates antigenic peptides from endogenously synthesized cellular and viral proteins5-10. These peptides bind to newly synthesized class I major histocompatibility complex molecules in the endoplasmic reticulum and peptide/class I complexes are then transported to the cell surface for presentation to cytotoxic T cells11,12. How these peptides are produced is unknown, although a modification that promotes ubiquitin-dependent degradation of a viral protein enhances its presentation with class I13 and indirect evidence suggests a role for proteolytic particles closely resembling and perhaps identical to the proteasome4,12,14,15. Using cells that exhibit a temperature-sensitive defect in ubiquitin conjugation, we report here that nonpermissive temperature inhibited class I-restricted presentation of ovalbumin introduced into the cytosol, but did not affect presentation of an ovalbumin peptide synthesized from a minigene. These results implicate the ubiquitin-dependent proteolytic pathway in the production of antigenic peptides.