biostudies-literatureShemorry ANIDDK NIH HHSNIGMS NIH HHS540-51https://www.ebi.ac.uk/biostudies/studies/S-EPMC3665649biostudies-literatureUnknown50(4)N(α)-terminal acetylation of cellular proteins was recently discovered to create specific degradation signals termed Ac/N-degrons and targeted by the Ac/N-end rule pathway. We show that Hcn1, a subunit of the APC/C ubiquitin ligase, contains an Ac/N-degron that is repressed by Cut9, another APC/C subunit and the ligand of Hcn1. Cog1, a subunit of the Golgi-associated COG complex, is also shown to contain an Ac/N-degron. Cog2 and Cog3, direct ligands of Cog1, can repress this degron. The subunit decoy technique was used to show that the long-lived endogenous Cog1 is destabilized and destroyed via its activated (unshielded) Ac/N-degron if the total level of Cog1 increased in a cell. Hcn1 and Cog1 are the first examples of protein regulation through the physiologically relevant transitions thMolecular cellControl of protein quality and stoichiometries by N-terminal acetylation and the N-end rule pathway.PMC3665649R56 DK039520DK039520R01 GM031530R01 DK039520GM031530R01 GM085371R37 DK039520GM085371Varshavsky AShemorry AHwang CSfalseControl of protein quality and stoichiometries by N-terminal acetylation and the N-end rule pathway.N(α)-terminal acetylation of cellular proteins was recently discovered to create specific degradation signals termed Ac/N-degrons and targeted by the Ac/N-end rule pathway. We show that Hcn1, a subunit of the APC/C ubiquitin ligase, contains an Ac/N-degron that is repressed by Cut9, another APC/C subunit and the ligand of Hcn1. Cog1, a subunit of the Golgi-associated COG complex, is also shown to contain an Ac/N-degron. Cog2 and Cog3, direct ligands of Cog1, can repress this degron. The subunit decoy technique was used to show that the long-lived endogenous Cog1 is destabilized and destroyed via its activated (unshielded) Ac/N-degron if the total level of Cog1 increased in a cell. Hcn1 and Cog1 are the first examples of protein regulation through the physiologically relevant transitions th2013-01-01T00:00:00Z2013 May2025-04-04T23:39:39.116Z2019-03-27T01:10:29ZS-EPMC36656492360311610.1016/j.molcel.2013.03.018