title: Control of protein quality and stoichiometries by N-terminal acetylation and the N-end rule pathway.
abstract: 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.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Shemorry
authors.forename: Cheol-Sang
authors.initials: CS
authors.lastname: Hwang
authors.forename: Alexander
authors.initials: A
authors.lastname: Varshavsky
mesh_terms: D000107:Acetylation; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D015151:Immunoblotting; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C112749:COG2 protein, S cerevisiae; C401396:COG3 protein, S cerevisiae; C468122:COG4 protein, S cerevisiae; C503913:Cog1 protein, S cerevisiae; D026901:Membrane Transport Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C086923:MOT2 protein, S cerevisiae; C066066:UBR1 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases