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Action of endogenous proteases on the distribution of tyrosinase isozymes in Harding–Passey mouse melanoma
Author(s) -
Martinez J. H.,
Solano F.,
Lozano J. A.
Publication year - 1989
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.290070105
Subject(s) - proteases , tyrosinase , biochemistry , cathepsin , enzyme , melanoma , melanosome , chemistry , cathepsin b , proteolysis , endogeny , isozyme , protease , microbiology and biotechnology , biology , melanin , cancer research
Abstract A high percentage of the total tyrosinase found in Harding–Passey mouse melanoma occurs as a soluble form. This paper shows that melanosomal tyrosinase can be solubilized by several endogenous proteases to yield active tyrosinase. This enzyme, once proteolitically solubilized, can be further degraded, leading to enzyme inactivation. The nature and specificity of the main proteases involved in the solubilization process change depending on the size and necrosis stage of the tumour. Cathepsin B could be the main protease responsible for the solubilization in small tumours (< 0·5 g). Large tumours are rich in necrotic cells, and cathepsin D and serine‐proteases are the main hydrolytic enzymes involved in the proteolytic action on mealanosomes. These results support the view that the high activity of tyrosinase found in the soluble fraction of malignant melanoma is mainly an artefact resulting from degradation of melanosomes by a variety of endogenous proteases, rather than the result of the actual occurrence of high levels of an independent cytosolic isozyme.