Organization and expression of the Cyr61 gene in normal human fibroblasts

We have examined the human Cyr61 gene and its expression in normal fibroblasts. The core promoter, second intron, and 3' untranslated region (UTR) are highly conserved between the human and mouse genes. Cyr61 expression was induced slightly slower but more transiently in human fibroblasts compared to Rat-2 fibroblasts. These differences may relate to the absence of a serum response element in the human Cyr61 promoter, and the presence of additional AU-rich elements within the 3' UTR. Cycloheximide causes accumulation of human Cyr61 RNA in the absence of growth factors, and EGF prevents decay of transcripts in actinomycin-D-treated cells, which suggests that induction by growth factors may partially involve mRNA stabilization. We detect an alternative RNA in serum-stimulated fibroblasts containing an in-frame deletion within exon 4 which disrupts the thrombospondin type 1 repeat. Constitutive expression of the full hCyr61 genomic DNA in rodent fibroblasts causes production of multiple protein species, whereas expression of hCyrDelta4 produces a single stable protein of the expected size. We also observed multiple hCyr61 protein species in normal fibroblasts following serum stimulation, indicating that Cyr61 may normally be produced as alternative isoforms.