Molecular cloning of human Hic-5, a potential regulator involved in signaltransduction and cellular senescence

By using differential display, we cloned the human counterpart of the murin e gene Hic-5 from senescent human keratinocytes. The full-length cDNA conta ined a short GC-stretch proceeding a consensus Kozak sequence followed by a single open reading frame of 1338 bp encoding a 461-amino acid protein wit h a predicted molecular weight of 50 kDa. The expression of this gene was p rominent in cells of epithelial origin but low or absent in lymphoid tissue s and hematopoietic cells. The deduced protein contained four LIM domains a t the carboxyl-terminal end and four LD motifs at the amino-terminal half, sharing high similarities with the focal adhesion protein paxillin. Hic-5 m ay therefore function, like paxillin, as a potential adapter for the recrui tment of structural and signaling molecules to certain subcellular sites or in focal adhesions. Isolation of the genomic sequence revealed that the ge ne covered a segment of 6 kb and spanned 11 exons from the translation init iation site ATG to the termination signal TGA. Fluorescent in situ hybridiz ation by using a human Hic-5 specific probe localized the gene to human chr omosome 16p11. Mol. Carcinog. 27:177-183, 2000. (C) 2000 Wiley-Liss, Inc.