N-terminal Met can trigger degradation

The N-end rule pathway for regulated protein degradation is crucial for many cellular functions. This pathway recognizes amino-terminal degradation signals (N-degrons) and promotes target protein ubiquitylation and degradation by the proteasome. There are two branches of this pathway in eukaryotes: the Arg/N-end rule pathway, which targets a specific set of unacetylated N-terminal residues that become exposed after co-translational cleavage of Met by specific enzymes, and the Ac/N-end rule pathway, which recognizes proteins with N^α-terminally acetylated residues; most proteins are N^α-terminally acetylated. Kim et al. find that the Arg/N-end rule pathway targets a much larger set of proteins than previously appreciated, as its dedicated E3 ubiquitin ligase, Ubr1, also recognizes unacetylated N-terminal Met followed by a hydrophobic residue.