| Hydrogen peroxide inducible clone-5 (Hic-5), also named transforming growth factor-beta1 induced transcript 1(TGFB1|1), TGF-beta stimulated clone-5 (TSC-5) or androgen receptor associated protein 55 (ARA55), is a LIM domain protein. It has LIM domains at its carboxyl half and LD motifs at its amino half, thus providing multiple protein-protein interfaces for interaction with a large number of proteins. Like its homologous protein paxillin, Hic-5 exists at focal adhesion sites and is involved in mediating signals from the extracellular matrix. Hic-5 also plays an important role in cell adhesion under physiological conditions. The association of Hic-5 and diverse focal adhesion proteins including kinases, that can be regulated by small G proteins, highlights its function as a scaffold protein for focal adhesion dynamics. The expression of Hic-5 is selective with a preference of distribution in mesenchymal and endothelial cells. Recent findings have shown aberrant Hic-5 expression in certain tissues under pathological conditions such as glomerulosclerosis and carcinogenesis. Hic-5 is involved in several signaling pathways, which indicates that it may be involved in regulating crosstalk between them. One signaling pathway that Hic-5 participates in is nuclear receptor signaling which is important for the transcriptional regulation of target genes. The regulation of nuclear receptor transcriptional activity renders Hic-5 a unique member of paxillin protein subfamily and a potential coactivator. Various strategies have been adopted to characterize the coactivator feature of Hic-5 over the past decade. Initial discovery by Yang et al. demonstrated that Hic-5 is a potential coactivator for a subset of nuclear receptors, which could partially localize in the nucleus and this research work will be discussed. |
