Maturation and degradation of β-galactosidase in the post-Golgi compartment are regulated by cathepsin B and a non-cysteine protease

• Published in: FEBS letters 1997-12, Vol.419 (2), p.231-234
• Main Authors: Okamura-Oho, Yuko, Zhang, Sunqu, Callahan, John W, Murata, Mitsuo, Oshima, Akihiro, Suzuki, Yoshiyuki
• Format: Article
• Language: English
• Subjects: 4-methylumbelliferone; 4MU; beta-Galactosidase - metabolism; CA074; CA074Me; carboxybenzoyl-l-argininyl-l-arginine 4-methyl-coumaryl-7-amide; Cathepsin B; Cathepsin B - metabolism; Cell Compartmentation; Cell Line; Chinese hamster ovary; CHO; Cysteine Proteinase Inhibitors - pharmacology; dimethyl sulfoxide; DMSO; E-64c; E64-c; E64-d; Fibroblasts - metabolism; Golgi Apparatus - metabolism; Humans; l-3-carboxy-2,3-trans-epoxypropionyl-leucylamide-(3-methyl)butane; Lysosome; Lysosomes - metabolism; M6P; mannose 6-phosphate; mannose 6-phosphate receptor; MPR; N-(1,3-transpropylcarbamoyloxirane-2-carbonyl)-1-isoleucyl-1-proline; N-(1,3-transpropylcarbamoyloxirane-2-carbonyl)-1-isoleucyl-1-proline methyl ester; N-[-(l-3-trans-ethoxycarbonyloxirane-2-carbonyl-l-leucyl]-3-methyl-butylamine; Protease inhibitor; Z-Arg-Arg-AMC; β-Galactosidase
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(97)01461-0

Lysosomal β-galactosidase precursor is processed to a mature form and associated with protective protein in lysosomes. In this study we used two cysteine protease proinhibitors, E64-d for cathepsins B, S, H, and L, and CA074Me for cathepsin B. They are converted intracellularly to active forms, E-64c and CA074, respectively. Both active compounds inhibited maturation of the exogenous β-galactosidase precursor, but E-64c did not inhibit further degradation to an inactive 50-kDa product. We concluded that cathepsin B participated exclusively in maturation of β-galactosidase, and a non-cysteine protease was involved in further degradation and inactivation of the enzyme molecule.