Biology:Cathepsin B

From HandWiki
Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Cathepsin B belongs to a family of lysosomal cysteine proteases known as the cysteine cathepsins and plays an important role in intracellular proteolysis.[1] In humans, cathepsin B is encoded by the CTSB gene.[2][3] Cathepsin B is upregulated in certain cancers, in pre-malignant lesions, and in various other pathological conditions.[4][5][6][7]

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.[8] At least five transcript variants encoding the same protein have been found for this gene.[9]

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.[10][11] 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,[12][13] and thus it has an essential position for the proteolysis of extracellular matrix components, intercellular communication disruption, and reduced protease inhibitor expression.[7]

Cells may become carcinogenic when cathepsin B is unregulated.[14]

Potential in cancer

Cathepsin B has been proposed as a potentially effective biomarker for a variety of cancers.[12][15] Overexpression of cathepsin B is correlated with invasive and metastatic cancers.[16]

Interactions

Cathepsin B has been shown to interact with:

Cathepsin B is inhibited by:

See also

References

  1. ↑ "Cathepsin B and cystatins: evidence for a role in cancer progression". Seminars in Cancer Biology 1 (2): 137–52. April 1990. PMID 2103490. 
  2. ↑ "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 83 (20): 7721–5. October 1986. doi:10.1073/pnas.83.20.7721. PMID 3463996. Bibcode: 1986PNAS...83.7721C. 
  3. ↑ "Human gastric adenocarcinoma cathepsin B: isolation and sequencing of full-length cDNAs and polymorphisms of the gene". Gene 139 (2): 163–9. February 1994. doi:10.1016/0378-1119(94)90750-1. PMID 8112600. 
  4. ↑ "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 177 (3): 586–97. September 2014. doi:10.1111/cei.12357. PMID 24749816. 
  5. ↑ "Early diagnosis of osteoarthritis using cathepsin B sensitive near-infrared fluorescent probes". Osteoarthritis and Cartilage 12 (3): 239–44. March 2004. doi:10.1016/j.joca.2003.11.005. PMID 14972341. 
  6. ↑ "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 285 (3): 2120–9. January 2010. doi:10.1074/jbc.M109.065813. PMID 19858192. 
  7. ↑ 7.0 7.1 "Cathepsin B Expression and the Correlation with Clinical Aspects of Oral Squamous Cell Carcinoma". PLOS ONE 11 (3): e0152165. 2016. doi:10.1371/journal.pone.0152165. PMID 27031837. Bibcode: 2016PLoSO..1152165Y. 
  8. ↑ "The structure of the mouse cathepsin B gene and its putative promoter". DNA and Cell Biology 10 (3): 159–68. April 1991. doi:10.1089/dna.1991.10.159. PMID 2012677. 
  9. ↑ "Entrez Gene: CTSB cathepsin B". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1508. 
  10. ↑ "Proteinases 1: lysosomal cysteine proteinases". Protein Profile 2 (14): 1581–643. 1995. PMID 8771190. 
  11. ↑ "Cathepsin B". The International Journal of Biochemistry & Cell Biology 29 (5): 715–20. May 1997. doi:10.1016/s1357-2725(96)00152-5. PMID 9251238. 
  12. ↑ 12.0 12.1 "uPAR and cathepsin B-mediated compartmentalization of JNK regulates the migration of glioma-initiating cells". Stem Cell Research 12 (3): 716–29. May 2014. doi:10.1016/j.scr.2014.02.008. PMID 24699410. 
  13. ↑ "Variable expression of cathepsin B and D correlates with highly invasive and metastatic phenotype of oral cancer". Human Pathology 31 (8): 931–7. August 2000. doi:10.1053/hupa.2000.9035. PMID 10987253. 
  14. ↑ Aggarwal, Neha; Sloane, Bonnie F. (June 2014). "Cathepsin B: Multiple roles in cancer". Proteomics. Clinical Applications 8 (5–6): 427–437. doi:10.1002/prca.201300105. ISSN 1862-8346. PMID 24677670. 
  15. ↑ "Cathepsin B promotes colorectal tumorigenesis, cell invasion, and metastasis". Molecular Carcinogenesis 55 (5): 671–87. May 2016. doi:10.1002/mc.22312. PMID 25808857. 
  16. ↑ "Over-expression of cathepsin B in hepatocellular carcinomas predicts poor prognosis of HCC patients". Molecular Cancer 15: 17. 20 February 2016. doi:10.1186/s12943-016-0503-9. PMID 26896959. 
  17. ↑ "Activation of cathepsin B, secreted by a colorectal cancer cell line requires low pH and is mediated by cathepsin D". International Journal of Cancer 67 (4): 547–54. August 1996. doi:10.1002/(SICI)1097-0215(19960807)67:4<547::AID-IJC14>3.0.CO;2-4. PMID 8759615. 
  18. ↑ 18.0 18.1 "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 42 (38): 11326–33. September 2003. doi:10.1021/bi030119v. PMID 14503883. 
  19. ↑ "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 37 (20): 7551–60. May 1998. doi:10.1021/bi980026r. PMID 9585570. 
  20. ↑ "Role of the single cysteine residue, Cys 3, of human and bovine cystatin B (stefin B) in the inhibition of cysteine proteinases". Protein Science 10 (9): 1729–38. September 2001. doi:10.1110/ps.11901. PMID 11514663. 
  21. ↑ "Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells". The Journal of Biological Chemistry 275 (17): 12806–12. April 2000. doi:10.1074/jbc.275.17.12806. PMID 10777578. 
  22. ↑ "B cell activation and the establishment of Epstein-Barr virus latency". The Journal of Experimental Medicine 168 (6): 2059–75. December 1988. doi:10.1084/jem.168.6.2059. PMID 2848918. 
  23. ↑ "Novel epoxysuccinyl peptides. Selective inhibitors of cathepsin B, in vitro". FEBS Letters 280 (2): 311–15. March 1991. doi:10.1016/0014-5793(91)80318-w. PMID 2013328. 

Further reading

External links



Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:Cathepsin_B&oldid=3656693"