Lactacystin, an inhibitor of the proteasome, blocks the degradation of a mutant precursor of glycosylphosphatidylinositol-linked protein in a pre-Golgi compartment.
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.
Oda
K
K
Department of Biochemistry, Niigata University School of Dentistry, Japan.
Ikehara
Y
Y
Omura
S
S
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006056:Golgi Apparatus / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007700:Kinetics; D018832:Molecular Chaperones / Q000096:biosynthesis / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology*; D046988:Proteasome Endopeptidase Complex; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism
D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D000091342:Endoplasmic Reticulum Chaperone BiP; D017261:Glycosylphosphatidylinositols; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D011993:Recombinant Fusion Proteins; C067713:lactacystin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine