Microtubule-mediated NF-kappaB activation in the XXXX signaling pathway.

@entity310 @entity4284 @entity1311 @entity3812 @entity10736
The microtubule cytoskeleton is known to play a role in cell structure and serve as a scaffold for a variety of active molecules in processes as diverse as motility and cell division. The literature on the role of microtubules in signal transduction, however, is marked by inconsistencies. We have investigated a well-studied signaling pathway, @entity310 -induced NF-kappaB activation, and found a connection between the stability of microtubules and the regulation of NF-kappaB signaling in C2C12 myotubes. When microtubules are stabilized by @entity1311 ( @entity1311 ), there is a strong induction of NF-kappaB even in the absence of @entity310 . Although there was no additive effect of @entity1311 and @entity310 on NF-kappaB activity suggesting a shared mechanism of activation, @entity1311 strongly induced the NF-kappaB reporter in the presence of a @entity10736 ( @entity10736 ) blocking antibody while @entity310 did not. Both @entity310 and @entity1311 induce the degradation of endogenous @entity4284 and either @entity1311 or @entity310 induction of NF-kappaB activity was blocked by inhibitors of NF-kappaB acting at different sites in the signaling pathway. Both @entity310 and @entity1311 strongly induce known NF-kappaB chemokine target genes. On the other hand, if microtubules are destabilized by @entity3812 , then the induction of NF-kappaB by @entity310 or @entity1311 is greatly reduced. Taken together, we surmise that the activity of microtubules is at the level of the @entity10736 intracellular domain. This phenomenon may indicate a new level of signaling organization in cell biology, actively created by the state of the cytoskeleton, and has ramifications for therapies where microtubule regulating drugs are used.
