Concomitant differentiation and partial proteasome inhibition trigger apoptosis in XXXX cells.

@entity268 @entity851 @entity7919 @entity19 @entity5 @entity5206 @entity5207 @entity521
Proteasome activity is essential during @entity268 -induced terminal differentiation of a @entity19 @entity521 cell line (NBP2). However, the mechanisms through which proteasome affects NBP2 differentiation have not been characterized. We hypothesized that proteasome is required to implement the differentiation-mediated effects on cell cycle, and its partial inhibition during differentiation may have adverse consequences. Here we show that partial inhibition of proteasome during @entity268 -induced differentiation of NBP2 cells causes apoptosis. Whereas differentiation induced @entity851 at G1 phase, partial proteasome inhibition during differentiation resulted in the accumulation of cells at G2M phase. Cell cycle data correlated with the level of cyclin-dependent kinase inhibitors @entity5207 and @entity7919 , and @entity5206 . While the level of @entity5207 and @entity7919 increased, the level of @entity5206 decreased upon differentiation. In contrast, cells treated with proteasome inhibitor in the presence of @entity268 -inducing agents showed increased levels of @entity5207 and @entity5206 early in the course of differentiation. However, the level of @entity5207 and @entity7919 , but not @entity5206 , decreased later during concomitant differentiation and partial proteasome inhibition when cells were undergoing apoptosis. Our data suggest that differentiation-mediated @entity851 is dependent on the temporal activity of cell cycle proteins. Partial inhibition of proteasome interferes with differentiation events partly by stabilizing cell cycle proteins and this triggers apoptosis. Thus, differentiating drugs combined with partial proteasome inhibition may impart higher therapeutic efficacy than differentiating agents alone for the treatment of @entity5 .
