The half-life of human procathepsin S.
Two processes, synthesis and degradation, contribute to the intracellular concentration of a protein. As most malignant tumors or tumor cell lines show elevated levels of proteinases, we studied the half-life of a cysteine proteinase, procathepsin S, in order to determine whether tumor cells can regulate their cathepsin concentration via changing the degradation rate of the enzyme. The following procathepsin S species were examined: wild-type procathepsin S in macrophages, recombinant procathepsin S in human embryonic kidney cells (HEK 293 cells), recombinant nonglycosylated procathepsin S in HEK 293 cells, wild-type procathepsin S in the established nonsmall cell lung carcinoma cell line 97TM1. The half-lives of both wild-type procathepsins S expressed in macrophages and in HEK 293 cells were 1 h, whereas that of procathepsin S in the tumor cell line was 2 h. Nonglycosylated procathepsin S was not processed. The degradation of mature cathepsin S proceeded with a half-life of 16-18 h. All cell lines studied secreted substantial amounts of procathepsin S into the culture medium. No further maturation of secreted procathepsin S has been observed in the culture medium. We suggest a disturbed sorting mechanism in tumor cells.
Nissler
K
K
Institute of Biochemistry, Klinikum, Friedrich-Schiller-University, Jena, Germany.
Strubel
W
W
Kreusch
S
S
Rommerskirch
W
W
Weber
E
E
Wiederanders
B
B
D002289:Carcinoma, Non-Small-Cell Lung; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D006207:Half-Life; D006801:Humans; D007668:Kidney; D007700:Kinetics; D008163:Luminescent Measurements; D008175:Lung Neoplasms; D008264:Macrophages / Q000201:enzymology*; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004792:Enzyme Precursors; D011994:Recombinant Proteins; D002403:Cathepsins; C028217:cathepsin S