Cathepsin B

Cathepsin B belongs to a family of lysosomal cysteine proteases known as the cysteine cathepsins and plays an important role in intracellular proteolysis. In humans, cathepsin B is encoded by the CTSB gene. Cathepsin B is upregulated in certain cancers, in pre-malignant lesions, and in various other pathological conditions.

The CTSB gene is located at chromosome 8p22, consisting of 13 exons. The promoter of CTSB gene contains a GC-rich region including many SP1 sites, which is similar to housekeeping genes. At least five transcript variants encoding the same protein have been found for this gene.

Cathepsin B is synthesized on the rough endoplasmic reticulum as a preproenzyme of 339 amino acids with a signal peptide of 17 amino acids. Procathepsin B of 43/46 kDa is then transported to the Golgi apparatus, where cathepsin B is formed. Mature cathepsin B is composed of a heavy chain of 25-26 kDa and a light chain of 5kDa, which are linked by a dimer of disulfide.

Cathepsin B may enhance the activity of other proteases, including matrix metalloproteinase, urokinase (serine protease urokinase plasminogen activator), and cathepsin D, and thus it has an essential position for the proteolysis of extracellular matrix components, intercellular communication disruption, and reduced protease inhibitor expression.

Cells may become carcinogenic when cathepsin B is unregulated.

Cathepsin B has been proposed as a potentially effective biomarker for a variety of cancers. Overexpression of cathepsin B is correlated with invasive and metastatic cancers.

Cathepsin B has been shown to be involved in the pathogenesis of pancreatitis, by prematurely activating the digestive enzyme trypsinogen within the pancreas, leading to autodigestion of acinar cells.

Cathepsin B has been shown to interact with: