Novel insights into cadherin processing by subtilisin-like convertases

FEBS Lett. 2003 Feb 11;536(1-3):203-8. doi: 10.1016/s0014-5793(02)03897-8.

Abstract

Proprotein convertases (PCs) are known to activate many important molecules and their overexpression plays a significant role in tumor progression. Only little is known about the involvement of PCs in the processing of cadherin adhesion molecules, which are potent tumor suppressors. Here we show in a baculovirus overexpression system that the desmosomal cadherins Dsg1 and Dsg3 are substrates for the PC furin. Accordingly, inhibition of PCs in differentiating mouse keratinocytes by alpha 1-anti-trypsin Portland (alpha 1-PDX) negatively interfered with pro-epithelial (proE)-cadherin processing, but unexpectedly also resulted in a dramatic reduction of E-cadherin, Dsg1 and Dsg3 protein and Dsg1 mRNA. Because loss of intercellular adhesion is a rate-limiting step in the transition from benign to malignant tumors, these results have significant implications for the use of PC inhibitors as possible therapeutic tools.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baculoviridae / genetics
  • Cadherins / chemistry
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cells, Cultured
  • Desmoglein 1
  • Desmoglein 3
  • Enzyme Inhibitors / pharmacology
  • Furin
  • Insecta / genetics
  • Keratinocytes / drug effects
  • Keratinocytes / enzymology
  • Mice
  • Proprotein Convertases
  • Protein Precursors / chemistry
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Subtilisins / metabolism*
  • alpha 1-Antitrypsin / pharmacology

Substances

  • Cadherins
  • DSG3 protein, human
  • Desmoglein 1
  • Desmoglein 3
  • Enzyme Inhibitors
  • Protein Precursors
  • alpha 1-Antitrypsin
  • alpha 1-antitrypsin Portland
  • Proprotein Convertases
  • Subtilisins
  • Furin