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.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Acetylation
-
Adaptor Proteins, Vesicular Transport / genetics
-
Adaptor Proteins, Vesicular Transport / metabolism
-
Golgi Apparatus / metabolism
-
Immunoblotting
-
Membrane Transport Proteins / genetics
-
Membrane Transport Proteins / metabolism
-
Models, Biological
-
Mutation
-
Protein Binding
-
Protein Processing, Post-Translational*
-
Proteolysis
-
Repressor Proteins
-
Saccharomyces cerevisiae / genetics
-
Saccharomyces cerevisiae / metabolism*
-
Saccharomyces cerevisiae Proteins / chemistry
-
Saccharomyces cerevisiae Proteins / genetics
-
Saccharomyces cerevisiae Proteins / metabolism*
-
Signal Transduction*
-
Ubiquitin-Protein Ligases / genetics
-
Ubiquitin-Protein Ligases / metabolism
-
Vesicular Transport Proteins / genetics
-
Vesicular Transport Proteins / metabolism
Substances
-
Adaptor Proteins, Vesicular Transport
-
COG2 protein, S cerevisiae
-
COG3 protein, S cerevisiae
-
COG4 protein, S cerevisiae
-
Cog1 protein, S cerevisiae
-
Membrane Transport Proteins
-
Repressor Proteins
-
Saccharomyces cerevisiae Proteins
-
Vesicular Transport Proteins
-
MOT2 protein, S cerevisiae
-
UBR1 protein, S cerevisiae
-
Ubiquitin-Protein Ligases