The N-end rule pathway: emerging functions and molecular principles of substrate recognition

Nat Rev Mol Cell Biol. 2011 Oct 21;12(11):735-47. doi: 10.1038/nrm3217.


The N-end rule defines the protein-destabilizing activity of a given amino-terminal residue and its post-translational modification. Since its discovery 25 years ago, the pathway involved in the N-end rule has been thought to target only a limited set of specific substrates of the ubiquitin-proteasome system. Recent studies have provided insights into the components, substrates, functions and structural basis of substrate recognition. The N-end rule pathway is now emerging as a major cellular proteolytic system, in which the majority of proteins are born with or acquire specific N-terminal degradation determinants through protein-specific or global post-translational modifications.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Animals
  • Humans
  • Models, Biological*
  • Models, Molecular
  • Protein Processing, Post-Translational / physiology*
  • Protein Stability
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proteins / chemistry
  • Proteins / metabolism
  • Signal Transduction
  • Static Electricity
  • Substrate Specificity


  • Amino Acids
  • Proteins