Serum response element-regulated transcription in the cell cycle: possible correlation with microtubule...

The transcriptional response to growth factors and other mitogenic signals is mediated by the serum response elements (SREs) located in the promoters of many immediate early genes, including the c-fos and beta-actin genes. We investigated SRE-regulated transcription in cell cycle-synchronized nuclei and found that a SRE-regulated reporter gene was transcribed actively during G1 and, surprisingly, during G2-M as well. One possible mechanism involved in the latter event is microtubule reorganization. Microtubule disassembly is mimicked by microtubule-disrupting drugs, and we found that these drugs, including colchicine, nocodazole, and vinblastine, could activate SRE-dependent reporter genes, as well as the c-fos protooncogene, in asynchronously growing cells. Taken together, our results suggested a possible relationship between cytoplasmic microtubule dynamics and cell cycle gene expression. Although the detailed molecular mechanisms of drug action are not known, protein phosphorylations may be involved, since drug-induced stimulation could be abrogated by several protein kinase inhibitors. Furthermore, the overexpression of mitogen-activated protein kinase ERK1 could superinduce the stimulation of SRE-dependent reporter gene expression by colchicine and suggests that the microtubule disassembly signal may be transduced by microtubule-associated kinases.