CYTOSKELETAL CONTROL OF GENE-EXPRESSION - DEPOLYMERIZATION OF MICROTUBULES ACTIVATES NF-KAPPA-B

Cell shape changes exert specific effects on gene expression. It has b een speculated that the cytoskeleton is responsible for converting cha nges in the cytoarchitecture to effects on gene transcription. However , the signal transduction pathways responsible for cytoskeletal-nuclea r communication remained unknown. We now provide evidence that a varie ty of agents and conditions that depolymerize microtubules activate th e sequence-specific transcription factor NF-B-kappa and induce NFkappa B-dependent gene expression. These effects are caused by depolymerizat ion of microtubule because they are blocked by the microtubule-stabili zing agent taxol. In nonstimulated cells, the majority of NF-B-kappa r esides in the cytosplasm as a complex with its inhibitor IkappaB. Upon cell stimulation, NF-B-kappa translocates to the nucleus with concomi tant degradation of IkappaB. We show that cold-induced depolymerizatio n of microtubules also leads to I kappa B degradation and activation o f NF-B-kappa. However, the activated factor remains in the cytoplasm a nd translocates to the nucleus only upon warming to 37 degrees C, thus revealing two distinct steps in NF-B-kappa activation. These findings establish a new role for NF-B-kappa in sensing changes in the state o f the cytoskeleton and converting them to changes in gene activity.