GENOMIC ORGANIZATION AND CHROMOSOME LOCALIZATION OF THE HUMAN CATHEPSIN-K GENE (CTSK)

Human cathepsin K is a recently described cysteine protease with high sequence homology to cathepsins S and L, members of the papain superfa mily of cysteine proteases. Cathepsin K is abundantly and selectively expressed in osteoclasts and may perform a specialized role in osteocl ast-mediated bone resorption. In the present study, the genomic organi zation and chromosomal localization of human cathepsin K (HGMW-approve d symbol CTSK) were determined. Intron-exon boundaries were identified by PCR on human genomic DNA, and subsequently a P1 genomic clone cont aining the full-length gene was isolated. Cathepsin K spans approximat ely 12.1 kb of genomic DNA and is composed of eight exons and seven in trons. The genomic organization of cathepsin K is similar to that of c athepsins S and L. The gene was mapped to chromosome 1q21 by fluoresce nce in situ hybridization. Primer walking on the P1 genomic clone iden tified 1108 bp of 5' flanking sequence and 459 bp of 3' flanking seque nce. Ribonuclease protection assay and 5' RACE indicated a single tran scriptional start site 49 bp upstream of the initiator Met codon. Anal ysis of the 5' flanking region indicates that this gene lacks canonica l TATA and CAAT boxes and contains multiple potential transcription re gulatory sites. The characterization of the cathepsin K gene and its p romoter may provide valuable insights not only into its osteoclast-sel ective expression, but also into the molecular mechanisms responsible for osteoclast activation. (C) 1997 Academic Press.