PEPTIDYL ALDEHYDE INHIBITORS OF PROTEASOME INDUCE APOPTOSIS RAPIDLY IN MOUSE LYMPHOMA RVC CELLS

Proteases play an important role in regulation of apoptosis, To elucid ate the role of proteasome in apoptosis, we examined the effects of th e proteasome inhibitors, eucyl-gamma-t-butyl-L-glutamyl-L-alanyl-L-leu cinal and carbobenzoxy-L-leucyl-L-leucyl-L-norvalinal on RVC lymphoma cells, Cells exposed to the proteasome inhibitors arrested at G2/M pha se followed by internucleosomal DNA cleavage, chromatin condensation, and formation of apoptotic bodies dose- and time-dependently. Ubiquiti nated histone H2A levels decreased in the exposed cells, suggesting a relationship between deubiquitination of histone H2A and the chromatin disarray seen in apoptosis, Northern blots showed an increase in expr ession of polyubiquitin genes early in the incubation, These findings suggest that the ubiquitin-mediated proteasome-proteolytic system is i nvolved in regulating the cell cycle and apoptosis in RVC cells.