Transcriptional activation of the human rod cGMP-phosphodiesterase beta-subunit gene is mediated by an upstream AP-1 element.
AUTOR(ES)
Di Polo, A
RESUMO
During photoactivation retinal cGMP-phosphodiesterase (PDE) mediates signal transduction in the photoreceptor outer segments. Mutations in the beta-subunit gene of rod-specific PDE (beta-PDE) have been associated with inherited retinal degeneration in a number of species, including human. Here we have investigated the proximal upstream sequences that participate in transcriptional activation of this gene. Transient transfections demonstrated that the sequence from -72 to +53 bp contained sufficient information to direct high levels of gene expression in cells of retinal origin. Deletion or mutagenesis of an AP-1 motif present in this region caused 90-95% reduction in reporter gene expression. By gel mobility shift assay we demonstrated specific interactions between putative nuclear transcription factors and this AP-1 element. These findings indicate that the proximal AP-1 site in the human beta-PDE promoter is functionally relevant and necessary for transcriptional activation of this gene.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=146967Documentos Relacionados
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