Inhibition by acidic phospholipids of protein degradation by ER-60 protease, a novel cysteine protease, of endoplasmic reticulum

• Published in: FEBS letters Vol. 312; no. 1; pp. 83 - 86
• Main Authors: Urade, Reiko, Kito, Makoto
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 02.11.1992; Elsevier
• Subjects: 3-hydroxy-3-methylglutaryl coenzyme A; ALLM; ALLN; Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Apolipoprotein A-II - metabolism; Biological and medical sciences; bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane; bis-Tris; Calcium-Binding Proteins - metabolism; Calreticulin; Cysteine Endopeptidases - isolation & purification; Cysteine Endopeptidases - metabolism; Cysteine protease; Cysteine Proteinase Inhibitors - pharmacology; degradation; EGTA; Endoplasmic reticulum; Endoplasmic Reticulum - enzymology; Enzymes and enzyme inhibitors; ER-60 protease; ethyleneglycol bis(2-aminoethylether)tetraacetic acid; Fundamental and applied biological sciences. Psychology; HMG-CoA; Humans; Hydrolases; inhibition; Isomerases - metabolism; liver; Male; Molecular Sequence Data; N-acetyl-leucyl-leucyl-methioninal; N-acetyl-leucyl-leucyl-norleucinal; N-tosyl-l-lysyl chloromethyl ketone; N-tosyl-l-phenylalanyl chloromethyl ketone; phosphatidylcholine; phosphatidylethanolamine; phosphatidylinositol; phosphatidylinositol 4,5-bisphosphate; Phosphatidylinositol Diacylglycerol-Lyase; Phosphatidylinositols - pharmacology; phosphatidylserine; Phosphatidylserines - pharmacology; Phospholipid; phospholipids; Phospholipids - pharmacology; Phosphoric Diester Hydrolases - metabolism; PIP2; Protein Disulfide-Isomerases; proteinase ER-60; proteins; Rat; Rats; Rats, Sprague-Dawley; SDS-PAGE; Sequence Homology, Amino Acid; sodium dodecyl sulfate-polyacrylamide gel electrophoresis; Substrate Specificity; T cell antigen receptor; TCR; TLCK; TPCK; PIP 2; TCR; PS; TPCK; Rat; TLCK; Phospholipid; HMG-CoA; bis-Tris; ER-60 protease; ER; EGTA; SDS-PAGE; ALLM; PC; ALLN; Cysteine protease; PE; PI; Endoplasmic reticulum; Enzyme; Liver; Rodentia; Cysteine proteinase; In vitro; Proteins; Vertebrata; Mammalia; Enzymatic activity; Catabolism; Inhibition
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(92)81415-I

A protein (ER60) with sequence similarity to phosphoinositide-specific phospholipase C-α 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 cylosol and lysosomes.