The Structure of the Mouse Cathepsin B Gene and Its Putative Promoter

Abstract

The mouse cathepsin B gene and its flanking regions were cloned and characterized. The gene contains 10 exons and 9 introns spanning about 20 kb. Although the exon-intron organization of the mouse cathepsin B gene showed some similarity to the rat cathepsin H and L genes, significant differences were found. In particular, the highly conserved sequence that contains the catalytically active cysteine in these genes is split at different sites by an intron. As with other thiol proteinases, there is no obvious correspondence between the coding exons and structural or functional units within preprocathepsin B. These results suggest that the lysosomal thiol proteinase genes are evolutionarily ancient and that intron shifting has occurred subsequent to their divergence from a common ancestral form. The 5'-flanking region and exon 1 sequences in the mouse cathepsin B gene have a high GC content of approximately 72%. The 5'-flanking region also contains several potential Sp1 binding sites, but lacks TATA and CAAT motifs. These characteristics suggest that cathepsin B is a "housekeeping" gene and its transcription may be controlled by multiple transcription factors, including Sp1.

Cysteine Peptidases of Mammals: Their Biological Roles and Potential Effects in the Oral Cavity and Other Tissues in Health and Disease

“…Consistent with this ubiquitous pattern of expression, these genes lack the TATA box motifs normally found in highly regulated genes but frequently absent from constitutively expressed genes (Ishidoh et al, 1989a,b;Qian et al, 1991). However, there is significant variation in the levels of these enzymes and their ratios in different tissues and cells (e.g., Qian et al, 1989;Gong et al, 1993;Katunuma et al, 1993;Söderström et al, 1999).…”

Mosquito Cathepsin B-like Protease Involved in Embryonic Degradation of Vitellin Is Produced as a Latent Extraovarian Precursor

“…Due to its broad specificity, cathepsin B plays a key role in intracellular protein catabolism in the lysosomal system (1). Cathepsin B has been well characterized both enzymatically and molecularly (2)(3)(4)(5)(6)(7)(8)(9)(10). The mammalian cathepsin B has been implicated in tumor invasion, progression, and metastasis (11)(12)(13)(14)(15).…”

Molecular Cloning, Chromosomal Localization, and Expression of Murine Dipeptidyl Peptidase I

“…DPPI also shares one common intron insertion site with cathepsin B (intron 6-exon 7 for DPPI and intron 5-exon 6 for cathepsin B). In all four genes, the active site histidine and asparagine residues are found within one exon, although the exon on which they reside, and the positions of the intron-exon insertion sites, differ from gene to gene (44,47). These similarities suggest that these cysteine proteases arose from a common ancestral gene, but that their structures have evolved to include intron losses and insertions.…”

“…Cathepsins B and H both also span more than 20 kb, and comprise 10 and more than 12 exons, respectively (44,45). In contrast, cathepsin L is a relatively compact gene of 8.5 kb, comprising 8 exons (46).…”

“…DPPI, and cathepsins H and L share the common intron insertion position that isolates the exon containing the active site cysteine residue (47). This highly conserved domain is split by an intron in cathepsin B (44). DPPI also shares one common intron insertion site with cathepsin B (intron 6-exon 7 for DPPI and intron 5-exon 6 for cathepsin B).…”