Hershko A, Heller H, Eytan E, Kaklij G, Rose I A
Proc Natl Acad Sci U S A. 1984 Nov;81(22):7021-5. doi: 10.1073/pnas.81.22.7021.
Previous studies suggest that the conjugation of ubiquitin to NH2 groups of proteins is required for protein breakdown. We now show that the selective modification of NH2-terminal alpha-NH2 groups of globin and lysozyme prevents their degradation by the ubiquitin proteolytic system from reticulocytes. The conjugation by ubiquitin of epsilon-NH2 groups of lysine residues, usually seen in multiples, was also inhibited in alpha-NH2-blocked proteins. Naturally occurring N alpha-acetylated proteins are not degraded by the ubiquitin system at a significant rate, while their nonacetylated counterparts from other species are good substrates. This suggests that one function of N alpha-acetylation of cellular proteins is to prevent their degradation by the ubiquitin system. alpha-NH2-blocked proteins can have their activity as substrates for degradation increased by incorporation of alpha-NH2 groups through the introduction of polyalanine side chains. Proteins in which most epsilon-NH2 groups are blocked but the alpha-NH2 group is free are degraded by the ubiquitin system, but at a reduced rate. It is therefore suggested that the exposure of a free NH2 terminus of proteins is required for degradation and probably initiates the formation of ubiquitin conjugates committed for degradation.
先前的研究表明，蛋白质分解需要泛素与蛋白质的氨基结合。我们现在表明，对珠蛋白和溶菌酶的氨基末端α-氨基进行选择性修饰可阻止它们被来自网织红细胞的泛素蛋白水解系统降解。赖氨酸残基的ε-氨基通常以多个形式存在的泛素结合在α-氨基被封闭的蛋白质中也受到抑制。天然存在的Nα-乙酰化蛋白质不会被泛素系统以显著速率降解，而来自其他物种的非乙酰化对应物则是良好的底物。这表明细胞蛋白质的Nα-乙酰化的一个功能是防止它们被泛素系统降解。α-氨基被封闭的蛋白质可以通过引入聚丙氨酸侧链并入α-氨基来增加其作为降解底物的活性。大多数ε-氨基被封闭但α-氨基游离的蛋白质会被泛素系统降解，但速率会降低。因此，有人提出蛋白质游离氨基末端的暴露是降解所必需的，并且可能启动了用于降解的泛素缀合物的形成。
