Research Article

N-Terminal Acetylation of Cellular Proteins Creates Specific Degradation Signals

See allHide authors and affiliations

Science  28 Jan 2010:
1183147
DOI: 10.1126/science.1183147

Abstract

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 Ala, Val, Ser, Thr, and 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. Here, we found, using the yeast Saccharomyces cerevisiae, 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 comprise a prevalent class of degradation signals in cellular proteins.