The non-classical export routes: FGF1 and IL-1alpha point the way

J Cell Sci. 2003 Dec 15;116(Pt 24):4871-81. doi: 10.1242/jcs.00872.

Abstract

Non-classical protein release independent of the ER-Golgi pathway has been reported for an increasing number of proteins lacking an N-terminal signal sequence. The export of FGF1 and IL-1alpha, two pro-angiogenic polypeptides, provides two such examples. In both cases, export is based on the Cu2+-dependent formation of multiprotein complexes containing the S100A13 protein and might involve translocation of the protein across the membrane as a 'molten globule'. FGF1 and IL-1alpha are involved in pathological processes such as restenosis and tumor formation. Inhibition of their export by Cu2+ chelators is thus an effective strategy for treatment of several diseases.

Publication types

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

MeSH terms

  • Animals
  • Cell Hypoxia / physiology
  • Cell Membrane / metabolism
  • Copper / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Fibroblast Growth Factor 1 / metabolism*
  • Humans
  • Interleukin-1 / metabolism*
  • Membrane Fluidity / physiology
  • Models, Structural
  • Neovascularization, Pathologic / metabolism
  • Protein Sorting Signals / physiology*
  • Protein Transport
  • S100 Proteins

Substances

  • Interleukin-1
  • Protein Sorting Signals
  • S100 Proteins
  • S100A13 protein, human
  • Fibroblast Growth Factor 1
  • Copper