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pubmed:abstractText |
We established that such stress agent as antibiotic anisomycin was capable at very low concentrations to activate transcription of immediate-early c-fos gene, which generally was under negative control in fibroblasts transformed by E1A and cHa-ras oncogenes. Activation of c-fos gene is short-term reaching a maximum in 1 hour after anisomycin action then its transcription level declines that is typical for immediate-early genes. Transcription of two other examined immediate-early genes, c-jun and Egr-1, is at high enough level in this cell line, however its additional activation does take place under anisomycin action too. It is shown that in E1A + ras transformants, anisomycin induces MEK/ERK and JNK MAP kinase pathways ofsignal transduction whereas p38 kinase cascade is not activated. Using specific inhibitors of various MAP kinase cascades it has been shown for E1A + ras transformed cells that the anisomycin-induced transcription of c-fos gene is mainly adjusted through MEK/ERK kinase pathway while high level of c-jun gene transcription is supported by activity of JNK kinases. Even at higher concentration, anisomycin does not lead finally to accumulation of acetylated forms of core histones, in particular H3 histone therefore the transcriptional activation of immediate-early genes induced by anisomycin is not bound apparently with decompactization of chromatin structure in the region of promoters of these genes.
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