Cloning of Mouse Dab2ip Gene,a Novel Member of the RasGTPase-Activating Protein Family and Characterization of Its Regulatory Region in Ptostate

Disabled homolog 2 (Drosophila) interacting protein (DAB2IP/Dab2IP) is a member of the GTPase-activating protein for downregulating the Ras-mediated signal pathway and TNF-mediated apoptosis. The downregulation of human DAB2IP mRNA levels was detected in prostate cancer cells due to the epigenetic regulation. Here, we isolated a mouse Dab2ip gene with a highly homologous sequence to that of the human and rat gene and mapped it at chromosome 2B. The mDab2ip gene contains 14 exons and 13 introns and spans approximately 65 kb. Exon1 contains at least three splicing variants (Ia, Ib, and Ic). The deduced amino acid sequence of mouse Dab2IP encompasses 1065 residues containing several unique protein interaction motifs as well as a Ras-like GAP-related domain, which shares a high homology with both humans and rats. Data from real-time RT-PCR analysis revealed a diverse expression pattern of the mDab2ip gene in various organs, implying differential regulation of this gene from various tissues. We have mapped a 1.3-kb segment containing a 5′-upstream region from exon Ia as a promoter region (–147/+545) in prostatic epithelial cell lines(TRAMP-C); this region is highly GC-rich, and mDab2ip appears to be a TATA-less promoter. It appears that epigenetic regulation, particularly histone acetylation of the Dab2ip gene promoter, plays an important role in modulating its gene expression in the mouse prostate cancer cell.