The ubiquitin-proteasome pathway and pathogenesis of human diseases

Annu Rev Med. 1999;50:57-74. doi: 10.1146/


The ubiquitin-proteasome pathway plays a pivotal role in the degradation of short-lived and regulatory proteins important in a variety of basic cellular processes, including regulation of the cell cycle, modulation of cell surface receptors and ion channels, and antigen presentation. The pathway involves an enzymatic cascade through which multiple ubiquitin molecules are covalently attached to the protein substrate, which is then degraded by the 26S proteasome complex. The pathway has been implicated in several forms of malignancy, in the pathogenesis of several genetic diseases (including cystic fibrosis, Angelman's syndrome, and Liddle syndrome), in immune surveillance/viral pathogenesis, and in the pathology of muscle wasting. The molecular mechanisms that underlie these processes are being unraveled at present.

Publication types

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

MeSH terms

  • Antigen Presentation / physiology
  • Cell Cycle / physiology
  • Cell Physiological Phenomena
  • Disease / etiology*
  • Genetic Diseases, Inborn / etiology
  • Humans
  • Immune System Diseases / etiology
  • Ion Channels / physiology
  • Muscular Diseases / etiology
  • Neoplasms / etiology
  • Peptide Hydrolases / physiology*
  • Proteasome Endopeptidase Complex*
  • Proteins / metabolism
  • Receptors, Cell Surface / physiology
  • Ubiquitins / physiology*
  • Virus Diseases / etiology
  • Wasting Syndrome / etiology


  • Ion Channels
  • Proteins
  • Receptors, Cell Surface
  • Ubiquitins
  • Peptide Hydrolases
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease