Unlocking the code of 14-3-3

J Cell Sci. 2004 Apr 15;117(Pt 10):1875-84. doi: 10.1242/jcs.01171.

Abstract

One of the most striking 'rags to riches' stories in the protein world is that of 14-3-3, originally identified in 1967 as merely an abundant brain protein. The first clues that 14-3-3 would play an important role in cell biology came almost 25 years later when it was found to interact with various proto-oncogene proteins and signaling proteins. The subsequent identification of 14-3-3 as a phosphoserine/phosphothreonine-binding protein firmly established its importance in cell signaling. 14-3-3 family members are found in all eukaryotes - from plants to mammals - and more than 100 binding partners have been identified to date. The targets of 14-3-3 are found in all subcellular compartments and their functional diversity is overwhelming - they include transcription factors, biosynthetic enzymes, cytoskeletal proteins, signaling molecules, apoptosis factors and tumor suppressors. 14-3-3 binding can alter the localization, stability, phosphorylation state, activity and/or molecular interactions of a target protein. Recent studies now indicate that the serine/threonine protein phosphatases PP1 and PP2A are important regulators of 14-3-3 binding interactions, and demonstrate a role for 14-3-3 in controlling the translocation of certain proteins from the cytoplasmic and endoplasmic reticulum to the plasma membrane. New reports also link 14-3-3 to several neoplastic and neurological disorders, where it might contribute to the pathogenesis and progression of these diseases.

Publication types

  • Review

MeSH terms

  • 14-3-3 Proteins / metabolism
  • 14-3-3 Proteins / physiology*
  • Animals
  • Cytoskeleton / metabolism
  • Humans
  • Models, Biological
  • Models, Molecular
  • Neoplasms / metabolism
  • Neurodegenerative Diseases / metabolism
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Plant Proteins / metabolism
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins / physiology
  • Signal Transduction

Substances

  • 14-3-3 Proteins
  • Plant Proteins
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Phosphoprotein Phosphatases