Capecchi M R, Capecchi N E, Hughes S H, Wahl G M
Proc Natl Acad Sci U S A. 1974 Dec;71(12):4732-6. doi: 10.1073/pnas.71.12.4732.
The degradation rates of several missense mutants of hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) in mouse L cells are compared to those of the wild-type enzyme. Although the rates of total protein breakdown in the mutant cell lines are identical to that of the parental L cell line, defective molecules of hypoxanthine-guanine phosphoribosyltransferase present in the mutant cell lines are degraded much faster than the wild-type enzyme. The level of defective phosphoribosyltransferase molecules present in the mutant cell lines is inversely proportional to the breakdown rate. This observation indicates that the major factor determining the concentrations of the defective phosphoribosyltransferases is their specific degradation rate. These results strongly support the hypothesis that abnormal proteins are selectively degraded in mammalian cells.
将次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（EC 2.4.2.8）的几种错义突变体在小鼠L细胞中的降解速率与野生型酶的降解速率进行了比较。尽管突变细胞系中总蛋白质的分解速率与亲本L细胞系相同，但突变细胞系中存在的有缺陷的次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶分子的降解速度比野生型酶快得多。突变细胞系中存在的有缺陷的磷酸核糖转移酶分子水平与分解速率成反比。这一观察结果表明，决定有缺陷的磷酸核糖转移酶浓度的主要因素是它们的特定降解速率。这些结果有力地支持了异常蛋白质在哺乳动物细胞中被选择性降解的假说。
