Noncovalent complexes between the lysosomal proteinase cathepsin B and its propeptide account for stable, extracellular, high molecular mass forms of the enzyme.
Although the lysosomal cysteine proteinase cathepsin B is alkaline pH-labile, active, stable high molecular mass forms have been reported previously from the culture medium of human and murine mammary tumor explants and the sputum of patients with purulent bronchiectasis. A similar, catalytically active, high molecular mass form of recombinant human cathepsin B produced in yeast has now been found to represent a noncovalent complex between the 30-kDa single chain enzyme and its 6-kDa propeptide formed during autocatalytic maturation of the proenzyme (see accompanying article; Mach, L., Mort, J. S., and Glössl, J. (1994) J. Biol. Chem. 269, 13030-13035). Incubation of the complex under acidic conditions resulted in dissociation and degradation of the inhibitory propeptide leading to increased enzymatic activity, as also observed for partially purified cathepsin B isoenzymes from purulent sputum and mammary tumor explant media. The stabilization of the processed proteinase as a noncovalent complex with its proregion provides an important mechanism whereby extracellular cathepsin B can lie dormant until regional acidification mediates its activity.
Mach
L
L
Zentrum für Angewandte Genetik, Universität für Bodenkultur, Vienna, Austria.
Mort
J S
JS
Glössl
J
J
D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000201:enzymology; D002401:Cathepsin B / Q000235:genetics / Q000378:metabolism*; D003470:Culture Media; D004792:Enzyme Precursors / Q000378:metabolism*; D004795:Enzyme Stability; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013183:Sputum / Q000201:enzymology; D014407:Tumor Cells, Cultured
D003470:Culture Media; D004792:Enzyme Precursors; D007527:Isoenzymes; C057832:procathepsin B; D002401:Cathepsin B