Identification and analysis of Hic-5/ARA55 isoforms: Implications for integrin signaling and steroid hormone action

Hic-5/ARA55 is a LIM-only member of the paxillin superfamily. Conflicting reports have suggested that Hic-5/ARA55 can both repress and enhance a number of biological processes, including myogenesis and tumorigenesis. With two Hic-5 isoforms documented, we hypothesized that multiple Hic-5 isoforms may exist that have both overlapping and isoform-specific functions. To test this hypothesis, we performed an extensive analysis of Hic-5 transcripts in both cell lines and mouse tissues and found 12 distinct isoforms that fall into two sub-families. These isoforms are derived from both alternative splicing and alternative transcriptional start sites (TSS). Hic-5 expression is regulated in a temporally and spatially controlled manner in vivo. The identification of numerous Hic-5 isoforms suggests that Hic-5 subsumes a number of distinct roles in cells and may explain the range of biological responses attributed to Hic-5.