title: A possible role of ER-60 protease in the degradation of misfolded proteins in the endoplasmic reticulum.
abstract: Wild-type human lysozyme (hLZM) is secreted when expressed in mouse L cells, whereas misfolded mutant hLZMs are retained and eventually degraded in a pre-Golgi compartment (Omura, F., Otsu, M., Yoshimori, T., Tashiro, Y., and Kikuchi, M. (1992) Eur. J. Biochem. 210, 591-599). These misfolded mutant hLZMs are associated with protein disulfide isomerase (Otsu, M., Omura, F., Yoshimori, T., and Kikuchi, M. (1994) J. Biol. Chem. 269, 6874-6877). From the observation that this degradation is sensitive to cysteine protease inhibitors, such as N-acetyl-leucyl-leucyl-norleucinal and N-acetyl-leucyl-leucyl-methioninal, but not to the serine protease inhibitors, 1-chloro-3-tosylamido-7-amino-2-heptanone and (p-amidinophenyl)methanesulfonyl fluoride, it was suggested that some cysteine proteases are likely responsible for the degradation of abnormal proteins in the endoplasmic reticulum (ER). ER-60 protease (ER-60), an ER resident protein with cysteine protease activity (Urade, R., Nasu, M., Moriyama, T., Wada, K., and Kito, M. (1992) J. Biol. Chem. 267, 15152-15159), was found to associate with misfolded hLZMs, but not with the wild-type protein, in mouse L cells. Furthermore, denatured hLZM is degraded by ER-60 in vitro, whereas native hLZM is not. These results suggest that ER-60 could be a component of the proteolytic machinery for the degradation of misfolded mutant hLZMs in the ER.
authors.affiliation: Protein Engineering Research Institute, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Otsu
authors.forename: R
authors.initials: R
authors.lastname: Urade
authors.forename: M
authors.initials: M
authors.lastname: Kito
authors.forename: F
authors.initials: F
authors.lastname: Omura
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D007739:L Cells; D008715:Methionine / Q000378:metabolism; D051379:Mice; D009113:Muramidase / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D010446:Peptide Fragments / Q000302:isolation & purification; D017510:Protein Folding; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014162:Transfection
chemical_list: D010446:Peptide Fragments; D011994:Recombinant Proteins; D013462:Sulfur Radioisotopes; D008715:Methionine; D009113:Muramidase; D003546:Cysteine Endopeptidases; C077733:ER-60 protease