Control of Protein Quality and Stoichiometries by N-terminal Acetylation and the N-end Rule Pathway

Mol Cell. 2013 May 23;50(4):540-51. doi: 10.1016/j.molcel.2013.03.018. Epub 2013 Apr 18.

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.

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