Interaction of Hic-5, A Senescence-related Protein, with Focal Adhesion Kinase

Abstract

Hydrogen peroxide-inducible clone (Hic)-5 is induced during the senescent process in human fibroblasts, and the overexpression of Hic-5 induces a senescence-like phenotype. Structurally, Hic-5 and paxillin, a 68-kDa cytoskeletal protein, share homology such as the LD motifs in the N-terminal half and the LIM domains in the C-terminal half. Here we show that Hic-5 binds to focal adhesion kinase (FAK) by its N-terminal domain, and is localized to focal adhesions by its C-terminal LIM domains. However, Hic-5 is not tyrosine phosphorylated either by the coexpressed FAK in COS cells or by integrin stimulation in 293T cells. Furthermore, overexpression of Hic-5 results in a decreased tyrosine phosphorylation of paxillin. These findings suggest that putative functions of Hic-5 are the recruitment of FAK to focal adhesions and a competitive inhibition of tyrosine phosphorylation of paxillin.