Cathepsin B

Structure

Gene

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.

Protein

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.

Function

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.

Potential in disease

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.

Interactions

Cathepsin B has been shown to interact with:

• CTSD
• CSTA,
• CSTB, and
• S100A10. Cathepsin B is inhibited by:
• Nitroxoline
• CA-074

References

References

1. (April 1990). "Cathepsin B and cystatins: evidence for a role in cancer progression". Seminars in Cancer Biology.
2. (October 1986). "Nucleotide and predicted amino acid sequences of cloned human and mouse preprocathepsin B cDNAs". Proceedings of the National Academy of Sciences of the United States of America.
3. (February 1994). "Human gastric adenocarcinoma cathepsin B: isolation and sequencing of full-length cDNAs and polymorphisms of the gene". Gene.
4. (September 2014). "Role of cathepsin B in regulating migration and invasion of fibroblast-like synoviocytes into inflamed tissue from patients with rheumatoid arthritis". Clinical and Experimental Immunology.
5. (March 2004). "Early diagnosis of osteoarthritis using cathepsin B sensitive near-infrared fluorescent probes". Osteoarthritis and Cartilage.
6. (January 2010). "Cathepsin B-mediated autophagy flux facilitates the anthrax toxin receptor 2-mediated delivery of anthrax lethal factor into the cytoplasm". The Journal of Biological Chemistry.
7. (2016). "Cathepsin B Expression and the Correlation with Clinical Aspects of Oral Squamous Cell Carcinoma". PLOS ONE.
8. (April 1991). "The structure of the mouse cathepsin B gene and its putative promoter". DNA and Cell Biology.
9. "Entrez Gene: CTSB cathepsin B".
10. (1995). "Proteinases 1: lysosomal cysteine proteinases". Protein Profile.
11. (May 1997). "Cathepsin B". The International Journal of Biochemistry & Cell Biology.
12. (May 2014). "uPAR and cathepsin B-mediated compartmentalization of JNK regulates the migration of glioma-initiating cells". Stem Cell Research.
13. (August 2000). "Variable expression of cathepsin B and D correlates with highly invasive and metastatic phenotype of oral cancer". Human Pathology.
14. (June 2014). "Cathepsin B: multiple roles in cancer". Proteomics. Clinical Applications.
15. (May 2016). "Cathepsin B promotes colorectal tumorigenesis, cell invasion, and metastasis". Molecular Carcinogenesis.
16. (February 2016). "Over-expression of cathepsin B in hepatocellular carcinomas predicts poor prognosis of HCC patients". Molecular Cancer.
17. (May 2019). "Early Intra-Acinar Events in Pathogenesis of Pancreatitis". Gastroenterology.
18. (April 2020). "Roles of Autophagy and Pancreatic Secretory Trypsin Inhibitor in Trypsinogen Activation in Acute Pancreatitis". Pancreas.
19. (May 2001). "Towards specific functions of lysosomal cysteine peptidases: phenotypes of mice deficient for cathepsin B or cathepsin L". Biological Chemistry.
20. (August 1996). "Activation of cathepsin B, secreted by a colorectal cancer cell line requires low pH and is mediated by cathepsin D". International Journal of Cancer.
21. (May 1998). "The role of Gly-4 of human cystatin A (stefin A) in the binding of target proteinases. Characterization by kinetic and equilibrium methods of the interactions of cystatin A Gly-4 mutants with papain, cathepsin B, and cathepsin L". Biochemistry.
22. (September 2003). "Grafting of features of cystatins C or B into the N-terminal region or second binding loop of cystatin A (stefin A) substantially enhances inhibition of cysteine proteinases". Biochemistry.
23. (September 2001). "Role of the single cysteine residue, Cys 3, of human and bovine cystatin B (stefin B) in the inhibition of cysteine proteinases". Protein Science.
24. (April 2000). "Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells". The Journal of Biological Chemistry.
25. (December 1988). "B cell activation and the establishment of Epstein-Barr virus latency". The Journal of Experimental Medicine.
26. (March 1991). "Novel epoxysuccinyl peptides. Selective inhibitors of cathepsin B, in vitro". FEBS Letters.