Cloning, genomic organization, and chromosomal localization of human cathepsin L

• Published in: The Journal of biological chemistry Vol. 268; no. 2; pp. 1039 - 1045
• Main Authors: CHAUHAN, S. S, POPESCU, N. C, RAY, D, FLEISCHMANN, R, GOTTESMAN, M. M, TROEN, B. R
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 15.01.1993
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Cathepsin L; Cathepsins - genetics; chromosome 9; Chromosome Banding; Chromosome Mapping; Chromosomes, Human, Pair 9; Cloning, Molecular; Cysteine Endopeptidases; Endopeptidases; Exons; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Enzymologic; genes; Genes. Genome; Genetic Vectors; Humans; Introns; Isoenzymes - genetics; Karyotyping; KB Cells; Lymphocytes - enzymology; man; mapping; Mice; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; nucleotide sequence; Oligodeoxyribonucleotides; Polymerase Chain Reaction; predictions; Restriction Mapping; RNA, Messenger - biosynthesis; Sequence Homology, Nucleic Acid; Tumor Cells, Cultured; Human; Cathepsin L; Gene; Nucleotide sequence; Enzyme; Isozyme; Gene expression; Localization; Tumor cell
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)54038-2

Cathepsin L is a lysosomal cysteine protease whose expression and secretion is induced by malignant transformation, growth factors, and tumor promoters. Many human tumors express high levels of cathepsin L, which is a broad spectrum protease with potent elastase and collagenase activities. Two published human cathepsin L cDNA sequences differ only in their 5'-untranslated regions. In this study, we demonstrate the concurrent expression of two distinct human cathepsin L mRNAs (hCATL-A and hCATL-B) in adenocarcinoma, hepatoma, and renal cancer cell lines. Cloning of the human cathepsin L gene by polymerase chain reaction amplification of genomic DNA and subsequent sequencing reveals that hCATL-A and hCATL-B mRNAs are encoded by a single gene. The 3' end of the first intron contains the 5' portion of hCATL-B and is contiguous to the second exon of the gene. These data suggest either the possibility of alternative splicing or the presence of a second promoter within the first intron of the hCATL gene. We mapped the hCATL gene to chromosome 9q21-22. Sequencing of both the mouse and human cathepsin L genes demonstrates almost complete conservation of exon and intron position, but significant divergence in intron structure, possibly reflecting differences in regulation of expression of the mouse and human cathepsin L genes.