Control 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 that shield and unshield natural Ac/N-degrons. This mechanistically straightforward circuit can employ the demonstrated conditionality of Ac/N-degrons to regulate subunit stoichiometries and other aspects of protein quality control.
Mesh Terms:
Acetylation, Adaptor Proteins, Vesicular Transport, Golgi Apparatus, Immunoblotting, Membrane Transport Proteins, Models, Biological, Mutation, Protein Binding, Protein Processing, Post-Translational, Proteolysis, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Ubiquitin-Protein Ligases, Vesicular Transport Proteins
Acetylation, Adaptor Proteins, Vesicular Transport, Golgi Apparatus, Immunoblotting, Membrane Transport Proteins, Models, Biological, Mutation, Protein Binding, Protein Processing, Post-Translational, Proteolysis, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction, Ubiquitin-Protein Ligases, Vesicular Transport Proteins
Mol. Cell
Date: May. 23, 2013
PubMed ID: 23603116
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