Figure 7

Model describing the interplay between Nt-acetylation, ubiquitination and protein stability. Based on the substrates studied, our data suggest that there are multiple classes of proteins that differ with regards to the impact of Nt-acetylation on protein stability, and its interplay with ubiquitination. Class I proteins, which include wild-type (WT) Bcl-B, are heavily modified by K48-linked ubiquitin chains targeting the substrate for proteasomal degradation. For Class I proteins, ubiquitination is the main determinant of protein stability and there is no impact of Nt-acetylation. Class II proteins are Class I proteins for which lysine ubiquitination is somehow prevented, like for a lysineless Bcl-B mutant (KR). Nt-acetylation inhibits degradation of Class II proteins by preventing ubiquitin conjugation to the N-terminus. Class III proteins might carry ubiquitin, but this does not function as a strong degradation signal. HA-GFP and p16 are Class III proteins. For these substrates, Nt-acetylation enhances protein stability by a mechanism that is independent of ubiquitination. Published literature^21,40,41 suggests the existence of Class IV proteins, which are stabilized by Nt-acetylation because it prevents recognition by E3 ubiquitin ligases.