Lactacystin, an inhibitor of the proteasome, blocks the degradation of a mutant precursor of glycosylphosphatidylinositol-linked protein in a pre-Golgi compartment

Biochem Biophys Res Commun. 1996 Feb 27;219(3):800-5. doi: 10.1006/bbrc.1996.0314.

Abstract

When transiently expressed in the COS-1 cell, a mutant chimeric protein with an uncleavable glycosylphosphatidylinositol (GPI) -anchor signal failed to be modified by GPI and undergoes rapid degradation in a pre-Golgi compartment. Among several protease inhibitors, 3,4-dichloroisocoumarin and N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal, potent inhibitors of the proteasome, strongly inhibited the degradation of the mutant protein. Furthermore, lactacystin, a highly specific inhibitor of the proteasome, was found to block the degradation. These results suggest that the pre-Golgi degradation pathway is functionally linked to the proteolytic system dependent on the proteasome, which hitherto was believed to play a role mostly in the cytoplasm and nucleus.

Publication types

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

MeSH terms

  • Acetylcysteine / analogs & derivatives*
  • Acetylcysteine / pharmacology
  • Animals
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / metabolism*
  • Cell Line
  • Chlorocebus aethiops
  • Cysteine Endopeptidases / metabolism*
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Glycosylphosphatidylinositols / metabolism*
  • Golgi Apparatus / metabolism
  • Heat-Shock Proteins / metabolism
  • Kinetics
  • Molecular Chaperones / biosynthesis
  • Molecular Chaperones / metabolism*
  • Multienzyme Complexes / metabolism*
  • Protease Inhibitors / pharmacology*
  • Proteasome Endopeptidase Complex
  • Rats
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / metabolism

Substances

  • Carrier Proteins
  • Cysteine Proteinase Inhibitors
  • Glycosylphosphatidylinositols
  • Heat-Shock Proteins
  • Molecular Chaperones
  • Multienzyme Complexes
  • Protease Inhibitors
  • Recombinant Fusion Proteins
  • lactacystin
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex
  • Acetylcysteine
  • molecular chaperone GRP78