PROSOMES (PROTEASOMES) CHANGES DURING DIFFERENTIATION ARE RELATED TO THE TYPE OF INDUCER

The core of the 26S proteasome, the 20S prosome, is a highly organized multi-protein complex found in large amount in malignant cells. Diffe rentiation of several cell lines, including the monoblastic U937 and t he lymphoblastoid CCRF-CEM, is accompanied by a general decrease in th e prosome concentration when phorbol-myrirtic-acetate (PMA) and retino ic acid plus dihydroxyvitamine D3 (RAS-VD) are used. Incubation of U93 7 cells for three days with PMA or RA+VD causes differentiation, but t he resulting patterns of prosome labeling in the cell and on the plasm a membrane are not the same. In contrast, the same kind of prosome cha nges occur in U937 and CCRF-CEM cells when PMA is used as inducer. The intracellular distribution of prosomes is also linked to malignancy a nd differentiation. Prosomes are found in the nucleus and the cytoplas m of cancer cells; and treatment with RA+VD decreases the prosomes in the nucleus whereas PMA causes various prosome proteins changes. These results indicate that prosomes are important in cell regulation and i n the expression of malignancy.