The turnover kinetics of major histocompatibility complex peptides of human cancer cells
The turnover kinetics of major histocompatibility complex peptides of human cancer cells
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DOI：
10.1074/mcp.m500241-mcp200
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发表时间：
2006-02-01
影响因子：
7
通讯作者：
Admon, A
中科院分区：
文献类型：
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作者：
Milner, E;Barnea, E;Admon, A
由主要组织相容性复合体（MHC）呈递的肽来源于细胞蛋白质的降解。因此，这些肽（MHC肽组）的库应该与细胞蛋白质降解方案（降解组）比与细胞蛋白质组更好地相关。为了测试这种说法的有效性，并确定大多数MHC肽是否来源于短寿命蛋白质、缺陷核糖体产物或常规长寿命细胞蛋白质，我们平行分析了相同癌细胞中MHC肽和细胞蛋白质的周转动力学。分析进行了脉冲追踪实验的基础上，在组织培养中的稳定同位素标记，然后通过毛细管色谱和串联质谱。事实上，在相同细胞中观察到的蛋白质组和MHC肽组之间仅观察到有限的相关性。此外，对MHC肽的周转动力学的详细分析有助于将它们的起源分配给正常的、短寿命或长寿命的蛋白质或有缺陷的核糖体产物。此外，MHC肽周转动力学的分析有助于直接关注其源蛋白的降解方案中的异常。这些观察结果可以扩展到寻找癌症相关的蛋白质降解异常，包括那些导致肿瘤抑制因子和细胞周期调节蛋白丢失的异常。
Peptides presented by the major histocompatibility complex (MHC) are derived from the degradation of cellular proteins. Thus, the repertoire of these peptides ( the MHC peptidome) should correlate better with the cellular protein degradation scheme (the degradome) than with the cellular proteome. To test the validity of this statement and to determine whether the majority of MHC peptides are derived from short lived proteins, from defective ribosome products, or from regular long lived cellular proteins we analyzed in parallel the turnover kinetics of both MHC peptides and cellular proteins in the same cancer cells. The analysis was performed by pulse-chase experiments based on stable isotope labeling in tissue culture followed by capillary chromatography and tandem mass spectrometry. Indeed only a limited correlation was observed between the proteome and the MHC peptidome observed in the same cells. Moreover a detailed analysis of the turnover kinetics of the MHC peptides helped to assign their origin to normal, to short lived or long lived proteins, or to the defective ribosome products. Furthermore the analysis of the MHC peptides turnover kinetics helped to direct attention to abnormalities in the degradation schemes of their source proteins. These observations can be extended to search for cancer-related abnormalities in protein degradation, including those that lead to loss of tumor suppressors and cell cycle regulatory proteins.