Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Science. 2010 Feb 19;327(5968):973-7. doi: 10.1126/science.1183147. Epub 2010 Jan 28.
The retained N-terminal methionine (Met) residue of a nascent protein is often N-terminally acetylated (Nt-acetylated). Removal of N-terminal Met by Met-aminopeptidases frequently leads to Nt-acetylation of the resulting N-terminal alanine (Ala), valine (Val), serine (Ser), threonine (Thr), and cysteine (Cys) residues. Although a majority of eukaryotic proteins (for example, more than 80% of human proteins) are cotranslationally Nt-acetylated, the function of this extensively studied modification is largely unknown. Using the yeast Saccharomyces cerevisiae, we found that the Nt-acetylated Met residue could act as a degradation signal (degron), targeted by the Doa10 ubiquitin ligase. Moreover, Doa10 also recognized the Nt-acetylated Ala, Val, Ser, Thr, and Cys residues. Several examined proteins of diverse functions contained these N-terminal degrons, termed AcN-degrons, which are a prevalent class of degradation signals in cellular proteins.
新生蛋白质中保留的 N 端甲硫氨酸（Met）残基通常会被 N 端乙酰化（Nt-acetylated）。甲氨肽酶去除 N 端 Met 后，通常会导致生成的 N 端丙氨酸（Ala）、缬氨酸（Val）、丝氨酸（Ser）、苏氨酸（Thr）和半胱氨酸（Cys）残基被 Nt-乙酰化。尽管大多数真核生物蛋白质（例如，超过 80%的人类蛋白质）是共翻译 Nt-乙酰化的，但这种广泛研究的修饰的功能在很大程度上仍然未知。使用酵母酿酒酵母，我们发现 Nt-乙酰化的 Met 残基可以作为降解信号（degron），被 Doa10 泛素连接酶靶向。此外，Doa10 还识别 Nt-乙酰化的 Ala、Val、Ser、Thr 和 Cys 残基。几种不同功能的被检查蛋白含有这些 N 端降解信号，称为 AcN-degrons，它们是细胞蛋白中普遍存在的一类降解信号。
