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Gene Review

CTSB  -  cathepsin B

Homo sapiens

Synonyms: APP secretase, APPS, CPSB, Cathepsin B, Cathepsin B1
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Disease relevance of CTSB

  • We have found a novel amplicon at 8p22-23 that results in CTSB overexpression in esophageal adenocarcinoma [1].
  • Using RT-PCR (reverse transcription-polymerase chain reaction) and primer extension assays, CTSB mRNA species were found to differ among tissues and between a glioblastoma sample and a cell line derived from it [2].
  • These clones demonstrate 98% identity to overlapping regions of published human hepatoma and kidney CTSB cDNAs, but show some interesting differences from the published sequences in the 3'-untranslated region (3'-UTR) [3].
  • Similarly, simultaneous inhibition of CTSB/CTSL was followed by a significant amelioration of colitis [4].
  • Human cathepsin B (CTSB) is a proteolytic enzyme implicated in tumor invasion and metastasis [5].

Psychiatry related information on CTSB


High impact information on CTSB


Chemical compound and disease context of CTSB


Biological context of CTSB

  • The finding of an amplicon at 8p22-23 resulting in CTSB gene amplification and overexpression supports an important role for CTSB in esophageal adenocarcinoma and possibly in other tumors [1].
  • Four full-length cDNA clones coding for preprocathepsin B were isolated from a human gastric adenocarcinoma cDNA library (AGS 1-6-30-1) and analyzed for possible sequence modifications that might be linked to altered intracellular trafficking and secretion of cathepsin B (CTSB) in malignant tumors [19].
  • Thus, factors related to the cell differentiation and environment seem likely to determine the types of transcripts that are expressed which in turn could influence the overall steady-state level of CTSB mRNAs and their rate of translation [2].
  • The human CTSB gene is located on chromosome 8 and the alleles described here can potentially be used as markers in linkage and association studies of cancers and other diseases [5].
  • The S2 binding site specificity of this enzyme has been altered to mimic that of cathepsin B or L by the application of site-directed mutagenesis at these latter three positions in the cathepsin S sequence [20].

Anatomical context of CTSB

  • Positive mRNA signals were obtained in the cytoplasm tumor cells, macrophages, and fibroblasts in 77% for CTSB and 81% for CTSL, respectively [21].
  • These data provide evidence for the identity of the MCE as cathepsin B and suggest that this cleavage most likely takes place within lysosomes, perhaps as a result of specific lysosomal targeting sequences within the MARCKS primary sequence [22].
  • We further demonstrated that cathepsin B and cathepsin L were released from the lysosomes and catalytically active in the cytosol [23].
  • MMP-1, CB, and CL messenger RNA (mRNA) were expressed in the synovial membrane of all patients and were present throughout the lining layer, as well as in perivascular cellular infiltrates and endothelial cells in the sublining layer [24].
  • Biochemical analyses showed increased activity of cathepsin B and L in muscle specimens from the patients with rimmed vacuole formation [25].

Associations of CTSB with chemical compounds


Physical interactions of CTSB


Enzymatic interactions of CTSB


Co-localisations of CTSB

  • Moreover, these intracellular stainings of HA and CD44 were co-localized with immunodeposits for cathepsin B, a representative cysteine proteinase in lysosomes [38].
  • Cathepsin B colocalizes with granzyme A in both normal and I-cells indicating that lysosomal proteins can also use the Man-6-P receptor-independent pathway in these cells [39].

Regulatory relationships of CTSB


Other interactions of CTSB


Analytical, diagnostic and therapeutic context of CTSB


  1. A novel amplicon at 8p22-23 results in overexpression of cathepsin B in esophageal adenocarcinoma. Hughes, S.J., Glover, T.W., Zhu, X.X., Kuick, R., Thoraval, D., Orringer, M.B., Beer, D.G., Hanash, S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  2. Identification of two new exons and multiple transcription start points in the 5'-untranslated region of the human cathepsin-B-encoding gene. Berquin, I.M., Cao, L., Fong, D., Sloane, B.F. Gene (1995) [Pubmed]
  3. Human cathepsin B-encoding cDNAs: sequence variations in the 3'-untranslated region. Tam, S.W., Cote-Paulino, L.R., Peak, D.A., Sheahan, K., Murnane, M.J. Gene (1994) [Pubmed]
  4. Cathepsins B, L and D in inflammatory bowel disease macrophages and potential therapeutic effects of cathepsin inhibition in vivo. Menzel, K., Hausmann, M., Obermeier, F., Schreiter, K., Dunger, N., Bataille, F., Falk, W., Scholmerich, J., Herfarth, H., Rogler, G. Clin. Exp. Immunol. (2006) [Pubmed]
  5. A polymorphic marker for the human cathepsin B gene. MacKenzie, J.R., Mason, S.L., Hickford, J.G., Kohonen-Corish, M.R., Bickerstaffe, R. Mol. Cell. Probes (2001) [Pubmed]
  6. Cerebrospinal fluid levels of amyloid beta-protein in Alzheimer's disease: inverse correlation with severity of dementia and effect of apolipoprotein E genotype. Nitsch, R.M., Rebeck, G.W., Deng, M., Richardson, U.I., Tennis, M., Schenk, D.B., Vigo-Pelfrey, C., Lieberburg, I., Wurtman, R.J., Hyman, B.T. Ann. Neurol. (1995) [Pubmed]
  7. Alzheimer's disease amyloid beta-clipping enzyme (APP secretase): identification, purification, and characterization of the enzyme. Tagawa, K., Kunishita, T., Maruyama, K., Yoshikawa, K., Kominami, E., Tsuchiya, T., Suzuki, K., Tabira, T., Sugita, H., Ishiura, S. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  8. Cannibalism of live lymphocytes by human metastatic but not primary melanoma cells. Lugini, L., Matarrese, P., Tinari, A., Lozupone, F., Federici, C., Iessi, E., Gentile, M., Luciani, F., Parmiani, G., Rivoltini, L., Malorni, W., Fais, S. Cancer Res. (2006) [Pubmed]
  9. Increased cathepsin B activity in pancreatic juice from a patient with pancreatic cancer. Rinderknecht, H., Renner, I.G. N. Engl. J. Med. (1980) [Pubmed]
  10. A metalloproteinase inhibitor domain in Alzheimer amyloid protein precursor. Miyazaki, K., Hasegawa, M., Funahashi, K., Umeda, M. Nature (1993) [Pubmed]
  11. Tumor cell-platelet aggregation: induced by cathepsin B-like proteinase and inhibited by prostacyclin. Honn, K.V., Cavanaugh, P., Evens, C., Taylor, J.D., Sloane, B.F. Science (1982) [Pubmed]
  12. Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading. Riese, R.J., Wolf, P.R., Brömme, D., Natkin, L.R., Villadangos, J.A., Ploegh, H.L., Chapman, H.A. Immunity (1996) [Pubmed]
  13. Expression of Cathepsin B and L antigen and activity is associated with early colorectal cancer progression. Troy, A.M., Sheahan, K., Mulcahy, H.E., Duffy, M.J., Hyland, J.M., O'Donoghue, D.P. Eur. J. Cancer (2004) [Pubmed]
  14. Estrogen-induced lysosomal proteases secreted by breast cancer cells: a role in carcinogenesis? Rochefort, H., Capony, F., Garcia, M., Cavaillès, V., Freiss, G., Chambon, M., Morisset, M., Vignon, F. J. Cell. Biochem. (1987) [Pubmed]
  15. Cathepsin B- and L-like activities at local gingival sites of chronic periodontitis patients. Eley, B.M., Cox, S.W. Journal of clinical periodontology. (1991) [Pubmed]
  16. Chondrocyte hypertrophy and apoptosis induced by GROalpha require three-dimensional interaction with the extracellular matrix and a co-receptor role of chondroitin sulfate and are associated with the mitochondrial splicing variant of cathepsin B. Olivotto, E., Vitellozzi, R., Fernandez, P., Falcieri, E., Battistelli, M., Burattini, S., Facchini, A., Flamigni, F., Santi, S., Facchini, A., Borzi', R.M. J. Cell. Physiol. (2007) [Pubmed]
  17. Plasma membrane association of cathepsin B in human prostate cancer: biochemical and immunogold electron microscopic analysis. Sinha, A.A., Jamuar, M.P., Wilson, M.J., Rozhin, J., Sloane, B.F. Prostate (2001) [Pubmed]
  18. Displacement of the occluding loop by the parasite protein, chagasin, results in efficient inhibition of human cathepsin B. Redzynia, I., Ljunggren, A., Abrahamson, M., Mort, J.S., Krupa, J.C., Jaskolski, M., Bujacz, G. J. Biol. Chem. (2008) [Pubmed]
  19. Human gastric adenocarcinoma cathepsin B: isolation and sequencing of full-length cDNAs and polymorphisms of the gene. Cao, L., Taggart, R.T., Berquin, I.M., Moin, K., Fong, D., Sloane, B.F. Gene (1994) [Pubmed]
  20. Engineering the S2 subsite specificity of human cathepsin S to a cathepsin L- and cathepsin B-like specificity. Brömme, D., Bonneau, P.R., Lachance, P., Storer, A.C. J. Biol. Chem. (1994) [Pubmed]
  21. Prognostic impact of cysteine proteases cathepsin B and cathepsin L in pancreatic adenocarcinoma. Niedergethmann, M., Wostbrock, B., Sturm, J.W., Willeke, F., Post, S., Hildenbrand, R. Pancreas (2004) [Pubmed]
  22. Identification and characterization of cathepsin B as the cellular MARCKS cleaving enzyme. Spizz, G., Blackshear, P.J. J. Biol. Chem. (1997) [Pubmed]
  23. Cathepsin-dependent apoptosis triggered by supraoptimal activation of T lymphocytes: a possible mechanism of high dose tolerance. Michallet, M.C., Saltel, F., Flacher, M., Revillard, J.P., Genestier, L. J. Immunol. (2004) [Pubmed]
  24. Synovial tissue protease gene expression and joint erosions in early rheumatoid arthritis. Cunnane, G., FitzGerald, O., Hummel, K.M., Youssef, P.P., Gay, R.E., Gay, S., Bresnihan, B. Arthritis Rheum. (2001) [Pubmed]
  25. Strong immunoreactivity of cathepsin L at the site of rimmed vacuoles in diseased muscles. Jimi, T., Satoh, Y., Takeda, A., Shibuya, S., Wakayama, Y., Sugita, K. Brain (1992) [Pubmed]
  26. Tumor necrosis factor induces the loss of sphingosine kinase-1 by a cathepsin B-dependent mechanism. Taha, T.A., Kitatani, K., Bielawski, J., Cho, W., Hannun, Y.A., Obeid, L.M. J. Biol. Chem. (2005) [Pubmed]
  27. Generation of endostatin by matrix metalloproteinase and cathepsin from human limbocorneal epithelial cells cultivated on amniotic membrane. Ma, D.H., Yao, J.Y., Kuo, M.T., See, L.C., Lin, K.Y., Chen, S.C., Chen, J.K., Chao, A.S., Wang, S.F., Lin, K.K. Invest. Ophthalmol. Vis. Sci. (2007) [Pubmed]
  28. Cathepsin L activity in alveolar macrophages of rats: response to cigarette smoke. Lesser, M., Galicki, N., Cardozo, C., Gariola, C.G. Am. J. Respir. Cell Mol. Biol. (1989) [Pubmed]
  29. Cell surface complex of cathepsin B/annexin II tetramer in malignant progression. Mai, J., Waisman, D.M., Sloane, B.F. Biochim. Biophys. Acta (2000) [Pubmed]
  30. Human sputum cathepsin B degrades proteoglycan, is inhibited by alpha 2-macroglobulin and is modulated by neutrophil elastase cleavage of cathepsin B precursor and cystatin C. Buttle, D.J., Abrahamson, M., Burnett, D., Mort, J.S., Barrett, A.J., Dando, P.M., Hill, S.L. Biochem. J. (1991) [Pubmed]
  31. Urokinase receptor is a multifunctional protein: influence of receptor occupancy on macrophage gene expression. Rao, N.K., Shi, G.P., Chapman, H.A. J. Clin. Invest. (1995) [Pubmed]
  32. The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. Musil, D., Zucic, D., Turk, D., Engh, R.A., Mayr, I., Huber, R., Popovic, T., Turk, V., Towatari, T., Katunuma, N. EMBO J. (1991) [Pubmed]
  33. Crystal structure of cathepsin X: a flip-flop of the ring of His23 allows carboxy-monopeptidase and carboxy-dipeptidase activity of the protease. Guncar, G., Klemencic, I., Turk, B., Turk, V., Karaoglanovic-Carmona, A., Juliano, L., Turk, D. Structure (2000) [Pubmed]
  34. Cathepsin B efficiently activates the soluble and the tumor cell receptor-bound form of the proenzyme urokinase-type plasminogen activator (Pro-uPA). Kobayashi, H., Schmitt, M., Goretzki, L., Chucholowski, N., Calvete, J., Kramer, M., Günzler, W.A., Jänicke, F., Graeff, H. J. Biol. Chem. (1991) [Pubmed]
  35. Sphingosine kinase-1 is cleaved by cathepsin B in vitro: Identification of the initial cleavage sites for the protease. Taha, T.A., El-Alwani, M., Hannun, Y.A., Obeid, L.M. FEBS Lett. (2006) [Pubmed]
  36. Amyloid beta/A4 precursor protein (APP) processing in lysosomes. Tagawa, K., Maruyama, K., Ishiura, S. Ann. N. Y. Acad. Sci. (1992) [Pubmed]
  37. The role of extracellular matrix in the processing of the amyloid protein precursor of Alzheimer's disease. Small, D.H., Nurcombe, V., Clarris, H., Beyreuther, K., Masters, C.L. Ann. N. Y. Acad. Sci. (1993) [Pubmed]
  38. Cytochemical localization of hyaluronic acid in human synovium with special reference to its possible process of degradation. Asari, A., Kuriyama, S., Kominami, E., Uchiyama, Y. Arch. Histol. Cytol. (1995) [Pubmed]
  39. Granzymes A and B are targeted to the lytic granules of lymphocytes by the mannose-6-phosphate receptor. Griffiths, G.M., Isaaz, S. J. Cell Biol. (1993) [Pubmed]
  40. Mutant K-ras regulates cathepsin B localization on the surface of human colorectal carcinoma cells. Cavallo-Medved, D., Dosescu, J., Linebaugh, B.E., Sameni, M., Rudy, D., Sloane, B.F. Neoplasia (2003) [Pubmed]
  41. Abnormal cathepsin B activity in Batten disease. Dawson, G., Glaser, P.T. American journal of medical genetics. Supplement. (1988) [Pubmed]
  42. OSU-03012 promotes caspase-independent but PERK-, cathepsin B-, BID-, and AIF-dependent killing of transformed cells. Yacoub, A., Park, M.A., Hanna, D., Hong, Y., Mitchell, C., Pandya, A.P., Harada, H., Powis, G., Chen, C.S., Koumenis, C., Grant, S., Dent, P. Mol. Pharmacol. (2006) [Pubmed]
  43. Phorbol ester activation of a proteolytic cascade capable of activating latent transforming growth factor-betaL a process initiated by the exocytosis of cathepsin B. Guo, M., Mathieu, P.A., Linebaugh, B., Sloane, B.F., Reiners, J.J. J. Biol. Chem. (2002) [Pubmed]
  44. Degradation of laminin by human tumor cathepsin B. Lah, T.T., Buck, M.R., Honn, K.V., Crissman, J.D., Rao, N.C., Liotta, L.A., Sloane, B.F. Clin. Exp. Metastasis (1989) [Pubmed]
  45. Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells. Mai, J., Finley, R.L., Waisman, D.M., Sloane, B.F. J. Biol. Chem. (2000) [Pubmed]
  46. Insulin-like growth factor II receptor-mediated intracellular retention of cathepsin B is essential for transformation of endothelial cells by Kaposi's sarcoma-associated herpesvirus. Rose, P.P., Bogyo, M., Moses, A.V., Früh, K. J. Virol. (2007) [Pubmed]
  47. Nuclear localization of cystatin B, the cathepsin inhibitor implicated in myoclonus epilepsy (EPM1). Riccio, M., Di Giaimo, R., Pianetti, S., Palmieri, P.P., Melli, M., Santi, S. Exp. Cell Res. (2001) [Pubmed]
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