Cathepsin B belongs to afamily oflysosomalcysteine proteases known as thecysteine cathepsins and plays an important role in intracellular proteolysis.[5] In humans, cathepsin B is encoded by theCTSBgene.[6][7] Cathepsin B is upregulated in certain cancers, in pre-malignant lesions, and in various other pathological conditions.[8][9][10][11]
TheCTSB gene is located atchromosome 8p22, consisting of 13exons. The promoter of CTSB gene contains a GC-rich region including many SP1 sites, which is similar tohousekeeping genes.[12] At least five transcript variants encoding the same protein have been found for this gene.[13]
Cathepsin B is synthesized on therough endoplasmic reticulum as a preproenzyme of 339amino acids with a signal peptide of 17 amino acids.[14][15] Procathepsin B of 43/46 kDa is then transported to theGolgi 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, includingmatrix metalloproteinase,urokinase (serine protease urokinase plasminogen activator), andcathepsin D,[16][17] and thus it has an essential position for the proteolysis of extracellular matrix components, intercellular communication disruption, and reduced protease inhibitor expression.[11]
Cells may become carcinogenic when cathepsin B is unregulated.[18]
Cathepsin B has been proposed as a potentially effective biomarker for a variety ofcancers.[16][19] Overexpression of cathepsin B is correlated with invasive and metastatic cancers.[20]
^Qian F, Frankfater A, Chan SJ, Steiner DF (April 1991). "The structure of the mouse cathepsin B gene and its putative promoter".DNA and Cell Biology.10 (3):159–168.doi:10.1089/dna.1991.10.159.PMID2012677.
^Vigneswaran N, Zhao W, Dassanayake A, Muller S, Miller DM, Zacharias W (August 2000). "Variable expression of cathepsin B and D correlates with highly invasive and metastatic phenotype of oral cancer".Human Pathology.31 (8):931–937.doi:10.1053/hupa.2000.9035.PMID10987253.
^Saluja A, Dudeja V, Dawra R, Sah RP (May 2019). "Early Intra-Acinar Events in Pathogenesis of Pancreatitis".Gastroenterology.156 (7):1979–1993.doi:10.1053/j.gastro.2019.01.268.PMID30776339.
^Hirota M, Ohmuraya M, Hashimoto D, Suyama K, Sugita H, Ogawa M (April 2020). "Roles of Autophagy and Pancreatic Secretory Trypsin Inhibitor in Trypsinogen Activation in Acute Pancreatitis".Pancreas.49 (4):493–497.doi:10.1097/MPA.0000000000001519.PMID32282761.
^Reinheckel T, Deussing J, Roth W, Peters C (May 2001). "Towards specific functions of lysosomal cysteine peptidases: phenotypes of mice deficient for cathepsin B or cathepsin L".Biological Chemistry.382 (5):735–741.doi:10.1515/BC.2001.089.PMID11517926.
^abPavlova A, Björk I (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.42 (38):11326–11333.doi:10.1021/bi030119v.PMID14503883.
^Estrada S, Nycander M, Hill NJ, Craven CJ, Waltho JP, Björk I (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.37 (20):7551–7560.doi:10.1021/bi980026r.PMID9585570.
Yan S, Sloane BF (June 2003). "Molecular regulation of human cathepsin B: implication in pathologies".Biological Chemistry.384 (6):845–854.doi:10.1515/BC.2003.095.PMID12887051.S2CID27472370.
