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Published February 19, 2010 | Accepted Version
Journal Article Open

N-Terminal Acetylation of Cellular Proteins Creates Specific Degradation Signals


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 ^(Ac)N-degrons, which are a prevalent class of degradation signals in cellular proteins.

Additional Information

© 2010 American Association for the Advancement of Science. Received for publication 9 October 2009. Accepted for publication 12 January 2010. We thank J. Zhou (Caltech) for MS analyses and C. Brower for comments on the paper. We are grateful to members of the Varshavsky laboratory for their advice in the course of this study and particularly thank O. Batygin for her technical assistance. This work was supported by grants from NIH and the March of Dimes Foundation to A.V.

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