Proteolysis as a regulatory mechanism

Annu Rev Genet. 2004:38:709-24. doi: 10.1146/annurev.genet.38.072902.093416.


Proteases can play key roles in regulation by controlling the levels of critical components of, for example, signal transduction pathways. Proteolytic processing can remove regulatory proteins when they are not needed, while transforming others from the dormant into the biologically active state. The latter mechanism often involves a subsequent change of cellular localization such as the movement from the membrane to the nucleus. The investigation of these processes has revealed a new type of proteolytic activity, regulated intramembrane proteolysis, and a reversible switch in activity occurring in the HtrA family of serine proteases. The bacterial RseA and the human amyloid precursor processing pathways are used as models to review these novel principles that are evolutionarily conserved and have wide biological implications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amyloid Precursor Protein Secretases
  • Amyloid beta-Protein Precursor
  • Aspartic Acid Endopeptidases
  • Bacteria / metabolism
  • Bacterial Proteins / metabolism*
  • Carrier Proteins / metabolism*
  • Endopeptidases / metabolism
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / metabolism*
  • Evolution, Molecular
  • Humans
  • Membrane Proteins / metabolism*
  • Models, Genetic
  • Models, Molecular
  • Peptide Hydrolases / metabolism*
  • Periplasm / metabolism
  • Protease Nexins
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Cell Surface
  • Signal Transduction
  • Transcription Factors / metabolism*


  • Amyloid beta-Protein Precursor
  • Bacterial Proteins
  • Carrier Proteins
  • DegS protein, Bacteria
  • Escherichia coli Proteins
  • Membrane Proteins
  • Protease Nexins
  • Receptors, Cell Surface
  • RseA protein, E coli
  • Transcription Factors
  • Amyloid Precursor Protein Secretases
  • Endopeptidases
  • Peptide Hydrolases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human