title: Serum response element-regulated transcription in the cell cycle: possible correlation with microtubule reorganization.
abstract: 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.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, NanKang, Taipei, Taiwan, Republic of China.
authors.forename: S H
authors.initials: SH
authors.lastname: Liu
authors.forename: H H
authors.initials: HH
authors.lastname: Lee
authors.forename: J J
authors.initials: JJ
authors.lastname: Chen
authors.forename: C F
authors.initials: CF
authors.lastname: Chuang
authors.forename: S Y
authors.initials: SY
authors.lastname: Ng
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002467:Cell Nucleus / Q000502:physiology; D003078:Colchicine / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000648:ultrastructure*; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D000199:Actins; D016760:Proto-Oncogene Proteins c-fos; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003078:Colchicine