Inhibition by acidic phospholipids of protein degradation by ER-60 protease, a novel cysteine protease, of endoplasmic reticulum.
A protein (ER60) with sequence similarity to phosphoinositide-specific phospholipase C-alpha purified from rat liver endoplasmic reticulum (ER) degraded ER resident proteins and is really a protease [(1992) J. Biol. Chem. 265, 15152-15159]. Therefore, ER60 is called ER-60 protease. We now show that negatively charged phospholipids, phosphatidylinositol, phosphatidylinositol 4,5-bisphosphate and phosphatidylserine inhibit ER protein degradation by ER-60 protease. Phosphatidylcholine and phosphatidylethanolamine show no effect on the activity of ER-60 protease. With the use of protease inhibitors, ER-60 protease is shown to be a novel cysteine protease distinct from those of the cytosol and lysosomes.
Urade
R
R
Research Institute for Food Science, Kyoto University, Japan.
Kito
M
M
D000595:Amino Acid Sequence; D000818:Animals; D016633:Apolipoprotein A-II / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037282:Calreticulin; D003546:Cysteine Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D006801:Humans; D007535:Isomerases / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000494:pharmacology; D010718:Phosphatidylserines / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D019704:Protein Disulfide-Isomerases; D051381:Rats; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
D016633:Apolipoprotein A-II; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D015853:Cysteine Proteinase Inhibitors; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D010743:Phospholipids; D010727:Phosphoric Diester Hydrolases; D003546:Cysteine Endopeptidases; C077733:ER-60 protease; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D007535:Isomerases; D019704:Protein Disulfide-Isomerases