[Biochemical and molecular biological studies on beta-glucuronidase in myelogenous leukemic cells]

beta-Glucuronidase purified from normal human tissues (placenta, liver and spleen) and granulocytes was composed of 80 kilo-Dalton (kDa), 64 kDa and 18 kDa subunits. The enzyme from human myelogenous leukemic cells contained a 80 kDa subunit as a major component. Amino acid sequencing revealed that N-terminal regions of the 80 kDa from CML cells and the 18 kDa from placenta were identical, and the sequence of the 64 kDa from placenta was identical to the downstream sequence of Gly138 in the 80 kDa enzyme. Therefore, it is probable that the 80 kDa is a precursor form and the 64 kDa is a mature form that is derived by removal of N-terminal 18 kDa peptide (137 amino acids) from the precursor form. These observation simply that proteolytic processing of this enzyme is impaired in myelogenous leukemic cells. The possibility of impaired protease activity against the 80 kDa subunit in CML cells was excluded, since the 80 kDa was not susceptible to several protease sources from normal tissues (placenta and liver) and granulocytes under a variety of reaction conditions. In addition no mutation of the primary structure in myelogenous leukemic cells was detected through analysis of DNA encoding for a peptide, including Gly138 of the enzyme. Therefore, it is suggested that abnormal processing of beta-GUase in the myelogenous leukemic cells is due to alteration in transcriptional or translational step.