Max-Planck-Institute for Biochemistry, Am Klopferspitz 18, 82152 Munich-Martinsried, Germany.
J Proteome Res. 2011 Dec 2;10(12):5275-84. doi: 10.1021/pr101183k. Epub 2011 Nov 3.
The turnover of each protein in the mammalian proteome is a functionally important characteristic. Here, we employed high-resolution mass spectrometry to quantify protein dynamics in nondividing mammalian cells. The ratio of externally supplied versus endogenous amino acids to de novo protein synthesis was about 17:1. Using subsaturating SILAC labeling, we obtained accurate turnover rates of 4106 proteins in HeLa and 3528 proteins in C2C12 cells. Comparison of these human and mouse cell lines revealed a highly significant turnover correlation of protein orthologs and thus high species conservation. Functionally, we observed statistically significant trends for the turnover of phosphoproteins and gene ontology categories that showed extensive covariation between mouse and human. Likewise, the members of some protein complexes, such as the proteasome, have highly similar turnover rates. The high species conservation and the low complex variances thus imply great regulatory fine-tuning of protein turnover.
哺乳动物蛋白质组中每种蛋白质的周转率是一个功能上重要的特征。在这里，我们采用高分辨率质谱法来定量非分裂哺乳动物细胞中的蛋白质动力学。外源性与内源性氨基酸与从头合成蛋白质的比率约为 17:1。使用亚饱和 SILAC 标记，我们获得了 HeLa 细胞中 4106 种蛋白质和 C2C12 细胞中 3528 种蛋白质的准确周转率。将这些人和小鼠细胞系进行比较，发现蛋白质直系同源物的周转率具有高度显著的相关性，因此具有高度的物种保守性。从功能上看，我们观察到磷酸化蛋白质和基因本体论类别的周转率存在统计学上显著的趋势，这些类别在小鼠和人类之间表现出广泛的共变。同样，一些蛋白质复合物的成员，如蛋白酶体，具有非常相似的周转率。因此，高物种保守性和低复合物方差意味着蛋白质周转率的调控非常精细。
