The involvement of b-actin in the signaling of transmembrane TNF-a-mediated XXXX .

@entity137 @entity10733 @entity8186 @entity9134 @entity5398 @entity10736
Actin cytoskeleton has been shown to play a regulating role in several signaling pathways, and disruption of actin filament has been reported to increase sTNF-a-induced cell death. However, whether actin is involved in tmTNF-a-mediated @entity137 remains unclear. Here, we demonstrated that pretreatment of HL-60 with CytD or LatA to depolymerize actin significantly suppressed tmTNF-a-mediated apoptosis. Interestingly, tmTNF-a increased the actin immunoprecipitated by anti- @entity10733 but not anti- @entity10736 antibody, and disruption of the actin filament totally blocked this effect. In addition, @entity10736 knockdown by siRNA did not affect tmTNF-a-mediated @entity137 and the inhibitory effect of CytD, suggesting that the involvement of actin in the tmTNF-a-induced apoptosis is linked to the @entity10733 pathway. Our results revealed further that tmTNF-a signaled the inhibition of IkB degradation and NF-kB activity by recruiting @entity5398 to and uncoupling @entity9134 from the @entity10733 complex. Nevertheless, CytD totally reversed the tmTNF-a signaling and activated NF-kB by recruiting @entity9134 to and dissociating @entity5398 from the @entity10733 complex. Furthermore, tmTNF-a led to activation of @entity8186 by dissociation of cFLIP from @entity10733 and inhibition of the cFLIP expression. Activated @entity8186 cleft @entity5398 to suppress NF-kB activity and also mediated tmTNF-a-induced apoptosis. However, CytD blocked the tmTNF-a-induced uncoupling of cFLIP from @entity10733 and prevented @entity8186 activation and the resulting cleavage of @entity5398 , converting the signaling for tmTNF-a-mediated apoptosis into one for activating NF-kB to survive. These results suggest that the actin cytoskeleton functions in transmitting signals via @entity10733 to mediate tmTNF-a-induced apoptosis.
