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 AcN-degrons, which are a prevalent class of degradation signals in cellular proteins.
Hwang
Cheol-Sang
CS
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Shemorry
Anna
A
Varshavsky
Alexander
A
D000107:Acetylation; D000409:Alanine / Q000378:metabolism; D000595:Amino Acid Sequence; D003545:Cysteine / Q000378:metabolism; D006207:Half-Life; D008715:Methionine / Q000378:metabolism*; D055550:Protein Stability; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination; D014633:Valine / Q000378:metabolism
C062928:MATA2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine; D008715:Methionine; C091362:SSM4 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases; D014633:Valine; D003545:Cysteine; D000409:Alanine