Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Cathepsin B

  • Dora Cavallo-Medved
  • Bonnie F. Sloane
  • Kamiar Moin
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101523

Synonyms

 CatB;  CathB;  CB1;  CPSB;  CTSB;  EC 3.4.22.1

Historical Background

Cathepsin derives from the Greek word “kathepsein” (i.e., to digest) and was coined in 1929 to describe digestive peptidases that are active in a slightly acidic environment (Willstätter and Bamann 1929). Cathepsin B, originally named cathepsin B1, was the first and remains the best-characterized member of the C1 family of papain-like, lysosomal cysteine peptidases. First purified from human liver in 1973 (Barrett 1973), cathepsin B is ubiquitously expressed in most cell and tissue types. The first complete protein sequence for cathepsin B, isolated from rat liver, was reported in 1983 (Takio et al. 1983). The first cDNA sequences for cathepsin B were published in 1985 (San Segundo et al. 1985). Cathepsin B exhibits both endopeptidase and exopeptidase activities, which are modulated by its occluding loop (Illy et al. 1997) and blocked by endogenous inhibitors of cysteine cathepsins (Barrett 1986). The main...

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References

  1. Abd-Elrahman I, Meir K, Kosuge H, Ben-Nun Y, Weiss Sadan T, Rubinstein C, Samet Y, McConnell MV, Blum G. Characterizing cathepsin activity and macrophage subtypes in excised human carotid plaques. Stroke. 2016;47:1101–8.CrossRefPubMedGoogle Scholar
  2. Abdollahi A, Getts LA, Sonoda G, Miller PD, Taguchi T, Godwin AK, Testa JR, Hamilton TC. Genome scanning detects amplification of the cathepsin B gene (CtsB) in transformed rat ovarian surface epithelial cells. J Soc Gynecol Investig. 1999;6:32–40.PubMedCrossRefGoogle Scholar
  3. Abrahamson M, Alvarez-Fernandez M, Nathanson CM. Cystatins. Biochem Soc Symp. 2003;179–99.Google Scholar
  4. Aggarwal N, Sloane BF. Cathepsin B: multiple roles in cancer. Proteomics Clin Appl. 2014;8:427–37.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Almeida PC, Nantes IL, Chagas JR, Rizzi CC, Faljoni-Alario A, Carmona E, Juliano L, Nader HB, Tersariol IL. Cathepsin B activity regulation. Heparin-like glycosaminogylcans protect human cathepsin B from alkaline pH-induced inactivation. J Biol Chem. 2001;276:944–51.PubMedCrossRefGoogle Scholar
  6. Arkona C, Wiederanders B. Expression, subcellular distribution and plasma membrane binding of cathepsin B and gelatinases in bone metastatic tissue. Biol Chem. 1996;377:695–702.PubMedPubMedCentralGoogle Scholar
  7. Baici A, Lang A, Zwicky R, Muntener K. Cathepsin B in osteoarthritis: uncontrolled proteolysis in the wrong place. Semin Arthritis Rheum. 2005;34:24–8.PubMedCrossRefGoogle Scholar
  8. Balaji KN, Schaschke N, Machleidt W, Catalfamo M, Henkart PA. Surface cathepsin B protects cytotoxic lymphocytes from self-destruction after degranulation. J Exp Med. 2002;196:493–503.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Barrett AJ. Human cathepsin B1. Purification and some properties of the enzyme. Biochem J. 1973;131:809–22.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Barrett AJ. The cystatins: a diverse superfamily of cysteine peptidase inhibitors. Biomed Biochim Acta. 1986;45:1363–74.PubMedPubMedCentralGoogle Scholar
  11. Ben-Aderet L, Merquiol E, Fahham D, Kumar A, Reich E, Ben-Nun Y, Kandel L, Haze A, Liebergall M, Kosinska MK, Steinmeyer J, Turk B, Blum G, Dvir-Ginzberg M. Detecting cathepsin activity in human osteoarthritis via activity-based probes. Arthritis Res Ther. 2015;17:69.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Berardi S, Lang A, Kostoulas G, Horler D, Vilei EM, Baici A. Alternative messenger RNA splicing and enzyme forms of cathepsin B in human osteoarthritic cartilage and cultured chondrocytes. Arthritis Rheum. 2001;44:1819–31.PubMedCrossRefGoogle Scholar
  13. Berquin IM, Cao L, Fong D, Sloane BF. Identification of two new exons and multiple transcription start points in the 5′-untranslated region of the human cathepsin-B-encoding gene. Gene. 1995;159:143–9.PubMedCrossRefGoogle Scholar
  14. Berquin IM, Sloane BF. Cathepsin B expression in human tumors. In: Suzuki K, Bond JS, editors. Intracellular Protein Catabolism. New York: Plenum Press; 1995. p. 281–94.Google Scholar
  15. Berquin IM, Yan S, Katiyar K, Huang L, Sloane BF, Troen BR. Differentiating agents regulate cathepsin B gene expression in HL-60 cells. J Leukoc Biol. 1999;66:609–16.PubMedCrossRefGoogle Scholar
  16. Bestvater F, Dallner C, Spiess E. The C-terminal subunit of artificially truncated human cathepsin B mediates its nuclear targeting and contributes to cell viability. BMC Cell Biol. 2005;6:16.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Bian B, Mongrain S, Cagnol S, Langlois MJ, Boulanger J, Bernatchez G, Carrier JC, Boudreau F, Rivard N. Cathepsin B promotes colorectal tumorigenesis, cell invasion, and metastasis. Mol Carcinog. 2016;55:671–87.PubMedCrossRefGoogle Scholar
  18. Blum G, von Degenfeld G, Merchant MJ, Blau HM, Bogyo M. Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Nat Chem Biol. 2007;3:668–77.PubMedCrossRefGoogle Scholar
  19. Bojic L, Petelin A, Stoka V, Reinheckel T, Peters C, Turk V, Turk B. Cysteine cathepsins are not involved in Fas/CD95 signalling in primary skin fibroblasts. FEBS Lett. 2007;581:5185–90.PubMedCrossRefGoogle Scholar
  20. Brix K, Lemansky P, Herzog V. Evidence for extracellularly acting cathepsins mediating thyroid hormone liberation in thyroid epithelial cells. Endocrinology. 1996;137:1963–74.PubMedCrossRefGoogle Scholar
  21. Brzin J, Rogelj B, Popovic T, Strukelj B, Ritonja A. Clitocypin, a new type of cysteine proteinase inhibitor from fruit bodies of mushroom clitocybe nebularis. J Biol Chem. 2000;275:20104–9.PubMedCrossRefGoogle Scholar
  22. Buck MR, Karustis DG, Day NA, Honn KV, Sloane BF. Degradation of extracellular-matrix proteins by human cathepsin B from normal and tumour tissues. Biochem J. 1992;282(Pt 1):273–8.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Caglic D, Pungercar JR, Pejler G, Turk V, Turk B. Glycosaminoglycans facilitate procathepsin B activation through disruption of propeptide-mature enzyme interactions. J Biol Chem. 2007;282:33076–85.PubMedCrossRefGoogle Scholar
  24. Campo E, Munoz J, Miquel R, Palacin A, Cardesa A, Sloane BF, Emmert-Buck MR. Cathepsin B expression in colorectal carcinomas correlates with tumor progression and shortened patient survival. Am J Pathol. 1994;145:301–9.PubMedPubMedCentralGoogle Scholar
  25. Castiglioni T, Merino MJ, Elsner B, Lah TT, Sloane BF, Emmert-Buck MR. Immunohistochemical analysis of cathepsins D, B, and L in human breast cancer. Hum Pathol. 1994;25:857–62.PubMedCrossRefGoogle Scholar
  26. Cavallo-Medved D, Dosescu J, Linebaugh BE, Sameni M, Rudy D, Sloane BF. Mutant K-ras regulates cathepsin B localization on the surface of human colorectal carcinoma cells. Neoplasia. 2003;5:507–19.PubMedPubMedCentralCrossRefGoogle Scholar
  27. Cavallo-Medved D, Mai J, Dosescu J, Sameni M, Sloane BF. Caveolin-1 mediates the expression and localization of cathepsin B, pro-urokinase plasminogen activator and their cell-surface receptors in human colorectal carcinoma cells. J Cell Sci. 2005;118:1493–503.PubMedCrossRefGoogle Scholar
  28. Cavallo-Medved D, Rudy D, Blum G, Bogyo M, Caglic D, Sloane BF. Live-cell imaging demonstrates extracellular matrix degradation in association with active cathepsin B in caveolae of endothelial cells during tube formation. Exp Cell Res. 2009;315:1234–46.PubMedPubMedCentralCrossRefGoogle Scholar
  29. Cavallo-Medved D, Sloane BF. Cell-surface cathepsin B: understanding its functional significance. Curr Top Dev Biol. 2003;54:313–41.PubMedCrossRefGoogle Scholar
  30. Cavanaugh PG, Sloane BF, Bajkowski AS, Gasic GJ, Gasic TB, Honn KV. Involvement of a cathepsin B-like cysteine proteinase in platelet aggregation induced by tumor cells and their shed membrane vesicles. Clin Exp Metastasis. 1983;1:297–307.PubMedCrossRefGoogle Scholar
  31. Chamberlain CM, Ang LS, Boivin WA, Cooper DM, Williams SJ, Zhao H, Hendel A, Folkesson M, Swedenborg J, Allard MF, McManus BM, Granville DJ. Perforin-independent extracellular granzyme B activity contributes to abdominal aortic aneurysm. Am J Pathol. 2010;176:1038–49.PubMedPubMedCentralCrossRefGoogle Scholar
  32. Chen J, Tung CH, Mahmood U, Ntziachristos V, Gyurko R, Fishman MC, Huang PL, Weissleder R. In vivo imaging of proteolytic activity in atherosclerosis. Circulation. 2002;105:2766–71.PubMedCrossRefGoogle Scholar
  33. Czyzewska J, Guzinska-Ustymowicz K, Kemona A, Bandurski R. The expression of matrix metalloproteinase 9 and cathepsin B in gastric carcinoma is associated with lymph node metastasis, but not with postoperative survival. Folia Histochem Cytobiol. 2008;46:57–64.PubMedCrossRefGoogle Scholar
  34. Dalet-Fumeron V, Boudjennah L, Pagano M. Competition between plasminogen and procathepsin B as a probe to demonstrate the in vitro activation of procathepsin B by the tissue plasminogen activator. Arch Biochem Biophys. 1996;335:351–7.PubMedCrossRefGoogle Scholar
  35. Dalet-Fumeron V, Guinec N, Pagano M. In vitro activation of pro-cathepsin B by three serine proteinases: leucocyte elastase, cathepsin G, and the urokinase-type plasminogen activator. FEBS Lett. 1993;332:251–4.PubMedCrossRefGoogle Scholar
  36. Deussing J, Roth W, Saftig P, Peters C, Ploegh HL, Villadangos JA. Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation. Proc Natl Acad Sci USA. 1998;95:4516–21.PubMedPubMedCentralCrossRefGoogle Scholar
  37. Dive V, Paulick MG, McIntyre JO, Matrisian LM, Bogyo M. Activity-based imaging and biochemical profiling tools for analysis of the cancer degradome. In: Edwards D, Hoyer-Hansen G, Blasi F, Sloane BF, editors. The cancer degradome: proteases and cancer biology. New York: Springer; 2008. p. 101–35.CrossRefGoogle Scholar
  38. Edgington LE, Verdoes M, Bogyo M. Functional imaging of proteases: recent advances in the design and application of substrate-based and activity-based probes. Curr Opin Chem Biol. 2011;15:798–805.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Felbor U, Kessler B, Mothes W, Goebel HH, Ploegh HL, Bronson RT, Olsen BR. Neuronal loss and brain atrophy in mice lacking cathepsins B and L. Proc Natl Acad Sci USA. 2002;99:7883–8.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Fernandez PL, Farre X, Nadal A, Fernandez E, Peiro N, Sloane BF, Shi GP, Chapman HA, Campo E, Cardesa A. Expression of cathepsins B and S in the progression of prostate carcinoma. Int J Cancer. 2001;95:51–5.PubMedCrossRefGoogle Scholar
  41. Foekens JA, Kos J, Peters HA, Krasovec M, Look MP, Cimerman N, Meijer-van Gelder ME, Henzen-Logmans SC, van Putten WL, Klijn JG. Prognostic significance of cathepsins B and L in primary human breast cancer. J Clin Oncol. 1998;16:1013–21.PubMedCrossRefGoogle Scholar
  42. Fong D, Chan MM, Hsieh WT, Menninger JC, Ward DC. Confirmation of the human cathepsin B gene (CTSB) assignment to chromosome 8. Hum Genet. 1992;89:10–2.PubMedCrossRefGoogle Scholar
  43. Gao L, Fang YQ, Zhang TY, Ge B, Tang RJ, Huang JF, Jiang LM, Tan N. Acidic extracellular microenvironment promotes the invasion and cathepsin B secretion of PC-3 cells. Int J Clin Exp Med. 2015;8:7367–73.PubMedPubMedCentralGoogle Scholar
  44. Gocheva V, Zeng W, Ke D, Klimstra D, Reinheckel T, Peters C, Hanahan D, Joyce JA. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev. 2006;20:543–56.PubMedPubMedCentralCrossRefGoogle Scholar
  45. Gomez-Auli A, Hillebrand LE, Biniossek ML, Peters C, Reinheckel T, Schilling O. Impact of cathepsin B on the interstitial fluid proteome of murine breast cancers. Biochimie. 2016;122:88–98.PubMedCrossRefGoogle Scholar
  46. Gondi CS, Rao JS. Cathepsin B as a cancer target. Expert Opin Ther Targets. 2013;17:281–91.PubMedPubMedCentralCrossRefGoogle Scholar
  47. Gong Q, Chan SJ, Bajkowski AS, Steiner DF, Frankfater A. Characterization of the cathepsin B gene and multiple mRNAs in human tissues: evidence for alternative splicing of cathepsin B pre-mRNA. DNA Cell Biol. 1993;12:299–309.PubMedCrossRefGoogle Scholar
  48. Gopinath S, Malla R, Alapati K, Gorantla B, Gujrati M, Dinh DH, Rao JS. Cathepsin B and uPAR regulate self-renewal of glioma-initiating cells through GLI-regulated Sox2 and Bmi1 expression. Carcinogenesis. 2013;34:550–9.PubMedCrossRefGoogle Scholar
  49. Gopinathan A, Denicola GM, Frese KK, Cook N, Karreth FA, Mayerle J, Lerch MM, Reinheckel T, Tuveson DA. Cathepsin B promotes the progression of pancreatic ductal adenocarcinoma in mice. Gut. 2012;61:877–84.PubMedCrossRefGoogle Scholar
  50. Guicciardi ME, Deussing J, Miyoshi H, Bronk SF, Svingen PA, Peters C, Kaufmann SH, Gores GJ. Cathepsin B contributes to TNF-alpha-mediated hepatocyte apoptosis by promoting mitochondrial release of cytochrome c. J Clin Invest. 2000;106:1127–37.PubMedPubMedCentralCrossRefGoogle Scholar
  51. Guicciardi ME, Miyoshi H, Bronk SF, Gores GJ. Cathepsin B knockout mice are resistant to tumor necrosis factor-alpha-mediated hepatocyte apoptosis and liver injury: implications for therapeutic applications. Am J Pathol. 2001;159:2045–54.PubMedPubMedCentralCrossRefGoogle Scholar
  52. Guo M, Mathieu PA, Linebaugh B, Sloane BF, Reiners Jr JJ. Phorbol ester activation of a proteolytic cascade capable of activating latent transforming growth factor-betaL a process initiated by the exocytosis of cathepsin B. J Biol Chem. 2002;277:14829–37.PubMedCrossRefGoogle Scholar
  53. Hajjar KA, Jacovina AT, Chacko J. An endothelial cell receptor for plasminogen/tissue plasminogen activator. I Identity with annexin II. J Biol Chem. 1994;269:21191–7.PubMedPubMedCentralGoogle Scholar
  54. Halangk W, Lerch MM, Brandt-Nedelev B, Roth W, Ruthenbuerger M, Reinheckel T, Domschke W, Lippert H, Peters C, Deussing J. Role of cathepsin B in intracellular trypsinogen activation and the onset of acute pancreatitis. J Clin Invest. 2000;106:773–81.PubMedPubMedCentralCrossRefGoogle Scholar
  55. Hansen T, Petrow PK, Gaumann A, Keyszer GM, Eysel P, Eckardt A, Brauer R, Kriegsmann J. Cathepsin B and its endogenous inhibitor cystatin C in rheumatoid arthritis synovium. J Rheumatol. 2000;27:859–65.PubMedPubMedCentralGoogle Scholar
  56. Hashimoto Y, Kakegawa H, Narita Y, Hachiya Y, Hayakawa T, Kos J, Turk V, Katunuma N. Significance of cathepsin B accumulation in synovial fluid of rheumatoid arthritis. Biochem Biophys Res Commun. 2001;283:334–9.PubMedCrossRefGoogle Scholar
  57. Hasnain S, Hirama T, Huber CP, Mason P, Mort JS. Characterization of cathepsin B specificity by site-directed mutagenesis. Importance of Glu245 in the S2-P2 specificity for arginine and its role in transition state stabilization. J Biol Chem. 1993;268:235–40.PubMedPubMedCentralGoogle Scholar
  58. Honn KV, Timar J, Rozhin J, Bazaz R, Sameni M, Ziegler G, Sloane BF. A lipoxygenase metabolite, 12-(S)-HETE, stimulates protein kinase C-mediated release of cathepsin B from malignant cells. Exp Cell Res. 1994;214:120–30.PubMedCrossRefGoogle Scholar
  59. Hook G, Yu J, Toneff T, Kindy M, Hook V. Brain pyroglutamate amyloid-beta is produced by cathepsin B and is reduced by the cysteine protease inhibitor E64d, representing a potential Alzheimer’s disease therapeutic. J Alzheimers Dis. 2014;41:129–49.PubMedPubMedCentralCrossRefGoogle Scholar
  60. Hook V, Toneff T, Bogyo M, Greenbaum D, Medzihradszky KF, Neveu J, Lane W, Hook G, Reisine T. Inhibition of cathepsin B reduces beta-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate beta-secretase of Alzheimer’s disease. Biol Chem. 2005;386:931–40.PubMedCrossRefGoogle Scholar
  61. Hook VY, Kindy M, Hook G. Inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein. J Biol Chem. 2008;283:7745–53.PubMedCrossRefGoogle Scholar
  62. Hook VY, Kindy M, Reinheckel T, Peters C, Hook G. Genetic cathepsin B deficiency reduces beta-amyloid in transgenic mice expressing human wild-type amyloid precursor protein. Biochem Biophys Res Commun. 2009;386:284–8.PubMedPubMedCentralCrossRefGoogle Scholar
  63. Hughes SJ, Glover TW, Zhu XX, Kuick R, Thoraval D, Orringer MB, Beer DG, Hanash S. A novel amplicon at 8p22-23 results in overexpression of cathepsin B in esophageal adenocarcinoma. Proc Natl Acad Sci USA. 1998;95:12410–5.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Illy C, Quraishi O, Wang J, Purisima E, Vernet T, Mort JS. Role of the occluding loop in cathepsin B activity. J Biol Chem. 1997;272:1197–202.PubMedCrossRefGoogle Scholar
  65. Jane DT, Morvay LC, Koblinski J, Yan S, Saad FA, Sloane BF, Dufresne MJ. Evidence that E-box promoter elements and MyoD transcription factors play a role in the induction of cathepsin B gene expression during human myoblast differentiation. Biol Chem. 2002;383:1833–44.PubMedCrossRefGoogle Scholar
  66. Jedeszko C, Sloane BF. Cysteine cathepsins in human cancer. Biol Chem. 2004;385:1017–27.PubMedCrossRefGoogle Scholar
  67. Joyce JA, Baruch A, Chehade K, Meyer-Morse N, Giraudo E, Tsai FY, Greenbaum DC, Hager JH, Bogyo M, Hanahan D. Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell. 2004;5:443–53.PubMedCrossRefGoogle Scholar
  68. Kassam G, Le BH, Choi KS, Kang HM, Fitzpatrick SL, Louie P, Waisman DM. The p11 subunit of the annexin II tetramer plays a key role in the stimulation of t-PA-dependent plasminogen activation. Biochemistry. 1998;37:16958–66.PubMedCrossRefGoogle Scholar
  69. Kassam G, Manro A, Braat CE, Louie P, Fitzpatrick SL, Waisman DM. Characterization of the heparin binding properties of annexin II tetramer. J Biol Chem. 1997;272:15093–100.PubMedCrossRefGoogle Scholar
  70. Kim DE, Kim JY, Schellingerhout D, Shon SM, Jeong SW, Kim EJ, Kim WK. Molecular imaging of cathepsin B proteolytic enzyme activity reflects the inflammatory component of atherosclerotic pathology and can quantitatively demonstrate the antiatherosclerotic therapeutic effects of atorvastatin and glucosamine. Mol Imaging. 2009;8:291–301.PubMedCrossRefGoogle Scholar
  71. Kirschke H, Barrett AJ, Rawlings ND. Proteinases 1: lysosomal cysteine proteinases. Protein Profile. 1995;2:1581–643.PubMedPubMedCentralGoogle Scholar
  72. Kobayashi H, Schmitt M, Goretzki L, Chucholowski N, Calvete J, Kramer M, Gunzler WA, Janicke F, Graeff H. Cathepsin B efficiently activates the soluble and the tumor cell receptor-bound form of the proenzyme urokinase-type plasminogen activator (Pro-uPA). J Biol Chem. 1991;266:5147–52.PubMedPubMedCentralGoogle Scholar
  73. Kuliawat R, Arvan P. Distinct molecular mechanisms for protein sorting within immature secretory granules of pancreatic beta-cells. J Cell Biol. 1994;126:77–86.PubMedCrossRefGoogle Scholar
  74. Lemaire R, Flipo RM, Migaud H, Fontaine C, Huet G, Dacquembronne E, Lafyatis R. Alternative splicing of the 5′ region of cathepsin B pre-messenger RNA in rheumatoid synovial tissue. Arthritis Rheum. 1997;40:1540–2.PubMedCrossRefGoogle Scholar
  75. Lenarcic B, Krishnan G, Borukhovich R, Ruck B, Turk V, Moczydlowski E. Saxiphilin, a saxitoxin-binding protein with two thyroglobulin type 1 domains, is an inhibitor of papain-like cysteine proteinases. J Biol Chem. 2000;275:15572–7.PubMedCrossRefGoogle Scholar
  76. Lenarcic B, Ritonja A, Strukelj B, Turk B, Turk V. Equistatin, a new inhibitor of cysteine proteinases from Actinia equina, is structurally related to thyroglobulin type-1 domain. J Biol Chem. 1997;272:13899–903.PubMedCrossRefGoogle Scholar
  77. Lerch MM, Halangk W. Human pancreatitis and the role of cathepsin B. Gut. 2006;55:1228–30.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Li W, Dalen H, Eaton JW, Yuan XM. Apoptotic death of inflammatory cells in human atheroma. Arterioscler Thromb Vasc Biol. 2001;21:1124–30.PubMedCrossRefGoogle Scholar
  79. Li W, Yuan XM. Increased expression and translocation of lysosomal cathepsins contribute to macrophage apoptosis in atherogenesis. Ann NY Acad Sci. 2004;1030:427–33.PubMedCrossRefGoogle Scholar
  80. Li Z, Berk M, McIntyre TM, Gores GJ, Feldstein AE. The lysosomal-mitochondrial axis in free fatty acid-induced hepatic lipotoxicity. Hepatology. 2008;47:1495–503.PubMedPubMedCentralCrossRefGoogle Scholar
  81. Linebaugh BE, Sameni M, Day NA, Sloane BF, Keppler D. Exocytosis of active cathepsin B enzyme activity at pH 7.0, inhibition and molecular mass. Eur J Biochem. 1999;264:100–9.PubMedCrossRefGoogle Scholar
  82. Linke M, Jordans S, Mach L, Herzog V, Brix K. Thyroid stimulating hormone upregulates secretion of cathepsin B from thyroid epithelial cells. Biol Chem. 2002;383:773–84.PubMedCrossRefGoogle Scholar
  83. Liu J, Guo Q, Chen B, Yu Y, Lu H, Li YY. Cathepsin B and its interacting proteins, bikunin and TSRC1, correlate with TNF-induced apoptosis of ovarian cancer cells OV-90. FEBS Lett. 2006a;580:245–50.PubMedCrossRefGoogle Scholar
  84. Liu JP, Liu NS, Yuan HY, Guo Q, Lu H, Li YY. Human homologue of SETA binding protein 1 interacts with cathepsin B and participates in TNF-Induced apoptosis in ovarian cancer cells. Mol Cell Biochem. 2006b;292:189–95.PubMedCrossRefGoogle Scholar
  85. Liu S, Aaronson H, Mitola DJ, Leppla SH, Bugge TH. Potent antitumor activity of a urokinase-activated engineered anthrax toxin. Proc Natl Acad Sci USA. 2003;100:657–62.PubMedPubMedCentralCrossRefGoogle Scholar
  86. Lutgens SP, Cleutjens KB, Daemen MJ, Heeneman S. Cathepsin cysteine proteases in cardiovascular disease. FASEB J. 2007;21:3029–41.PubMedCrossRefGoogle Scholar
  87. Maciewicz RA, Wardale RJ, Wotton SF, Duance VC, Etherington DJ. Mode of activation of the precursor to cathepsin L: implication for matrix degradation in arthritis. Biol Chem Hoppe Seyler. 1990;371(Suppl):223–8.PubMedPubMedCentralGoogle Scholar
  88. Mai J, Finley Jr RL, Waisman DM, Sloane BF. Human procathepsin B interacts with the annexin II tetramer on the surface of tumor cells. J Biol Chem. 2000a;275:12806–12.PubMedCrossRefGoogle Scholar
  89. Mai J, Waisman DM, Sloane BF. Cell surface complex of cathepsin B/annexin II tetramer in malignant progression. Biochim Biophys Acta. 2000b;1477:215–30.PubMedCrossRefGoogle Scholar
  90. Majerus MA, Bibollet-Ruche F, Telliez JB, Wasylyk B, Bailleul B. Serum, AP-1 and Ets-1 stimulate the human ets-1 promoter. Nucleic Acids Res. 1992;20:2699–703.PubMedPubMedCentralCrossRefGoogle Scholar
  91. Mehtani S, Gong Q, Panella J, Subbiah S, Peffley DM, Frankfater A. In vivo expression of an alternatively spliced human tumor message that encodes a truncated form of cathepsin B. Subcellular distribution of the truncated enzyme in COS cells. J Biol Chem. 1998;273:13236–44.PubMedCrossRefGoogle Scholar
  92. Mirkovic B, Markelc B, Butinar M, Mitrovic A, Sosic I, Gobec S, Vasiljeva O, Turk B, Cemazar M, Sersa G, Kos J. Nitroxoline impairs tumor progression in vitro and in vivo by regulating cathepsin B activity. Oncotarget. 2015;6:19027–42.PubMedPubMedCentralCrossRefGoogle Scholar
  93. Mohamed MM, Cavallo-Medved D, Rudy D, Anbalagan A, Moin K, Sloane BF. Interleukin-6 increases expression and secretion of cathepsin B by breast tumor-associated monocytes. Cell Physiol Biochem. 2010;25:315–24.PubMedPubMedCentralCrossRefGoogle Scholar
  94. Mohamed MM, Sloane BF. Cysteine cathepsins: multifunctional enzymes in cancer. Nat Rev Cancer. 2006;6:764–75.PubMedCrossRefGoogle Scholar
  95. Moin K, Cao L, Day NA, Koblinski JE, Sloane BF. Tumor cell membrane cathepsin B. Biol Chem. 1998;379:1093–9.PubMedCrossRefGoogle Scholar
  96. Moon HY, Becke A, Berron D, Becker B, Sah N, Benoni G, Janke E, Lubejko ST, Greig NH, Mattison JA, Duzel E, van Praag H. Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function. Cell Metab. 2016;24:332–40.PubMedCrossRefPubMedCentralGoogle Scholar
  97. Mort JS, Buttle DJ. Cathepsin B. Int J Biochem Cell Biol. 1997;29:715–20.PubMedCrossRefGoogle Scholar
  98. Muntener K, Zwicky R, Csucs G, Baici A. The alternative use of exons 2 and 3 in cathepsin B mRNA controls enzyme trafficking and triggers nuclear fragmentation in human cells. Histochem Cell Biol. 2003;119:93–101.PubMedPubMedCentralGoogle Scholar
  99. Muntener K, Zwicky R, Csucs G, Rohrer J, Baici A. Exon skipping of cathepsin B: mitochondrial targeting of a lysosomal peptidase provokes cell death. J Biol Chem. 2004;279:41012–7.PubMedCrossRefGoogle Scholar
  100. Musil D, Zucic D, Turk D, Engh RA, Mayr I, Huber R, Popovic T, Turk V, Towatari T, Katunuma N, et al. The refined 2.15 A X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. EMBO J. 1991;10:2321–30.PubMedPubMedCentralCrossRefGoogle Scholar
  101. Nagler DK, Storer AC, Portaro FC, Carmona E, Juliano L, Menard R. Major increase in endopeptidase activity of human cathepsin B upon removal of occluding loop contacts. Biochemistry. 1997;36:12608–15.PubMedCrossRefGoogle Scholar
  102. Naudin C, Lecaille F, Chowdhury S, Krupa JC, Purisima E, Mort JS, Lalmanach G. The occluding loop of cathepsin B prevents its effective inhibition by human kininogens. J Mol Biol. 2010;400:1022–35.PubMedCrossRefGoogle Scholar
  103. Nycander M, Estrada S, Mort JS, Abrahamson M, Bjork I. Two-step mechanism of inhibition of cathepsin B by cystatin C due to displacement of the proteinase occluding loop. FEBS Lett. 1998;422:61–4.PubMedCrossRefGoogle Scholar
  104. Osuala KO, Sameni M, Shah S, Aggarwal N, Simonait ML, Franco OE, Hong Y, Hayward SW, Behbod F, Mattingly RR, Sloane BF. Il-6 signaling between ductal carcinoma in situ cells and carcinoma-associated fibroblasts mediates tumor cell growth and migration. BMC Cancer. 2015;15:584.PubMedPubMedCentralCrossRefGoogle Scholar
  105. Pavlova A, Krupa JC, Mort JS, Abrahamson M, Bjork I. Cystatin inhibition of cathepsin B requires dislocation of the proteinase occluding loop. Demonstration By release of loop anchoring through mutation of his110. FEBS Lett. 2000;487:156–60.PubMedCrossRefGoogle Scholar
  106. Reichenbach G, Starzinski-Powitz A, Doll M, Hrgovic I, Valesky EM, Kippenberger S, Bernd A, Kaufmann R, Meissner M. Ligand activation of peroxisome proliferator-activated receptor delta suppresses cathepsin B expression in human endothelial cells in a posttranslational manner. Exp Dermatol. 2012;21:751–7.PubMedCrossRefGoogle Scholar
  107. Reichenbach G, Starzinski-Powitz A, Sloane BF, Doll M, Kippenberger S, Bernd A, Kaufmann R, Meissner M. PPARalpha agonist Wy14643 suppresses cathepsin B in human endothelial cells via transcriptional, post-transcriptional and post-translational mechanisms. Angiogenesis. 2013;16:223–33.PubMedCrossRefGoogle Scholar
  108. Reinheckel T, Peters C, Kruger A, Turk B, Vasiljeva O. Differential Impact of Cysteine Cathepsins on Genetic Mouse Models of De novo Carcinogenesis: Cathepsin B as Emerging Therapeutic Target. Front Pharmacol. 2012;3:133.PubMedPubMedCentralCrossRefGoogle Scholar
  109. Rempel SA, Rosenblum ML, Mikkelsen T, Yan PS, Ellis KD, Golembieski WA, Sameni M, Rozhin J, Ziegler G, Sloane BF. Cathepsin B expression and localization in glioma progression and invasion. Cancer Res. 1994;54:6027–31.PubMedPubMedCentralGoogle Scholar
  110. Renko M, Pozgan U, Majera D, Turk D. Stefin A displaces the occluding loop of cathepsin B only by as much as required to bind to the active site cleft. FEBS J. 2010;277:4338–45.PubMedCrossRefGoogle Scholar
  111. Robey IF, Baggett BK, Kirkpatrick ND, Roe DJ, Dosescu J, Sloane BF, Hashim AI, Morse DL, Raghunand N, Gatenby RA, Gillies RJ. Bicarbonate increases tumor pH and inhibits spontaneous metastases. Cancer Res. 2009;69:2260–8.PubMedPubMedCentralCrossRefGoogle Scholar
  112. Roshy S, Sloane BF, Moin K. Pericellular cathepsin B and malignant progression. Cancer Metastasis Rev. 2003;22:271–86.PubMedCrossRefGoogle Scholar
  113. Rothberg JM, Bailey KM, Wojtkowiak JW, Ben-Nun Y, Bogyo M, Weber E, Moin K, Blum G, Mattingly RR, Gillies RJ, Sloane BF. Acid-mediated tumor proteolysis: contribution of cysteine cathepsins. Neoplasia. 2013;15:1125–37.PubMedPubMedCentralCrossRefGoogle Scholar
  114. Rothberg JM, Sameni M, Moin K, Sloane BF. Live-cell imaging of tumor proteolysis: impact of cellular and non-cellular microenvironment. Biochim Biophys Acta. 2012;1824:123–32.PubMedCrossRefGoogle Scholar
  115. Rozhin J, Sameni M, Ziegler G, Sloane BF. Pericellular pH affects distribution and secretion of cathepsin B in malignant cells. Cancer Res. 1994;54:6517–25.PubMedPubMedCentralGoogle Scholar
  116. Rozman J, Stojan J, Kuhelj R, Turk V, Turk B. Autocatalytic processing of recombinant human procathepsin B is a bimolecular process. FEBS Lett. 1999;459:358–62.PubMedCrossRefGoogle Scholar
  117. Ruan J, Zheng H, Rong X, Rong X, Zhang J, Fang W, Zhao P, Luo R. Over-expression of cathepsin B in hepatocellular carcinomas predicts poor prognosis of HCC patients. Mol Cancer. 2016;15:17.PubMedPubMedCentralCrossRefGoogle Scholar
  118. Sameni M, Elliott E, Ziegler G, Fortgens PH, Dennison C, Sloane BF. Cathepsin B and D are Localized at the Surface of Human Breast Cancer Cells. Pathol Oncol Res. 1995;1:43–53.PubMedCrossRefGoogle Scholar
  119. Sameni M, Moin K, Sloane BF. Imaging proteolysis by living human breast cancer cells. Neoplasia. 2000;2:496–504.PubMedPubMedCentralCrossRefGoogle Scholar
  120. San Segundo B, Chan SJ, Steiner DF. Identification of cDNA clones encoding a precursor of rat liver cathepsin B. Proc Natl Acad Sci USA. 1985;82:2320–4.PubMedPubMedCentralCrossRefGoogle Scholar
  121. Scorilas A, Fotiou S, Tsiambas E, Yotis J, Kotsiandri F, Sameni M, Sloane BF, Talieri M. Determination of cathepsin B expression may offer additional prognostic information for ovarian cancer patients. Biol Chem. 2002;383:1297–303.PubMedCrossRefGoogle Scholar
  122. Sendler M, Maertin S, John D, Persike M, Weiss FU, Kruger B, Wartmann T, Wagh P, Halangk W, Schaschke N, Mayerle J, Lerch MM. Cathepsin B Activity Initiates Apoptosis via Digestive Protease Activation in Pancreatic Acinar Cells and Experimental Pancreatitis. J Biol Chem. 2016;291:14717–31.PubMedPubMedCentralCrossRefGoogle Scholar
  123. Sensarn S, Zavaleta CL, Segal E, Rogalla S, Lee W, Gambhir SS, Bogyo M, Contag CH. A clinical wide-field fluorescence endoscopic device for molecular imaging demonstrating cathepsin protease activity in colon cancer. Mol Imaging Biol. 2016;18:820–9.PubMedPubMedCentralCrossRefGoogle Scholar
  124. Sevenich L, Schurigt U, Sachse K, Gajda M, Werner F, Muller S, Vasiljeva O, Schwinde A, Klemm N, Deussing J, Peters C, Reinheckel T. Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice. Proc Natl Acad Sci USA. 2010;107:2497–502.PubMedPubMedCentralCrossRefGoogle Scholar
  125. Sevenich L, Werner F, Gajda M, Schurigt U, Sieber C, Muller S, Follo M, Peters C, Reinheckel T. Transgenic expression of human cathepsin B promotes progression and metastasis of polyoma-middle-T-induced breast cancer in mice. Oncogene. 2011;30:54–64.PubMedCrossRefGoogle Scholar
  126. Sinha AA, Quast BJ, Wilson MJ, Fernandes ET, Reddy PK, Ewing SL, Gleason DF. Prediction of pelvic lymph node metastasis by the ratio of cathepsin B to stefin A in patients with prostate carcinoma. Cancer. 2002;94:3141–9.PubMedCrossRefGoogle Scholar
  127. Sloane BF, Moin K, Sameni M, Tait LR, Rozhin J, Ziegler G. Membrane association of cathepsin B can be induced by transfection of human breast epithelial cells with c-Ha-ras oncogene. J Cell Sci. 1994;107(Pt 2):373–84.PubMedPubMedCentralGoogle Scholar
  128. Sloane BF, Rozhin J, Johnson K, Taylor H, Crissman JD, Honn KV. Cathepsin B: association with plasma membrane in metastatic tumors. Proc Natl Acad Sci USA. 1986;83:2483–7.PubMedPubMedCentralCrossRefGoogle Scholar
  129. Szpaderska AM, Silberman S, Ahmed Y, Frankfater A. Sp1 regulates cathepsin B transcription and invasiveness in murine B16 melanoma cells. Anticancer Res. 2004;24:3887–91.PubMedPubMedCentralGoogle Scholar
  130. Takahashi T, Schmidt PG, Tang J. Novel carbohydrate structures of cathepsin B from porcine spleen. J Biol Chem. 1984;259:6059–62.PubMedPubMedCentralGoogle Scholar
  131. Takio K, Towatari T, Katunuma N, Teller DC, Titani K. Homology of amino acid sequences of rat liver cathepsins B and H with that of papain. Proc Natl Acad Sci USA. 1983;80:3666–70.PubMedPubMedCentralCrossRefGoogle Scholar
  132. Talukdar R, Sareen A, Zhu H, Yuan Z, Dixit A, Cheema H, George J, Barlass U, Sah R, Garg SK, Banerjee S, Garg P, Dudeja V, Dawra R, Saluja AK. Release of cathepsin B in cytosol causes cell death in acute pancreatitis. Gastroenterology. 2016;151:747–58.PubMedPubMedCentralCrossRefGoogle Scholar
  133. Tam SW, Cote-Paulino LR, Peak DA, Sheahan K, Murnane MJ. Human cathepsin B-encoding cDNAs: sequence variations in the 3′-untranslated region. Gene. 1994;139:171–6.PubMedCrossRefGoogle Scholar
  134. Tedelind S, Poliakova K, Valeta A, Hunegnaw R, Yemanaberhan EL, Heldin NE, Kurebayashi J, Weber E, Kopitar-Jerala N, Turk B, Bogyo M, Brix K. Nuclear cysteine cathepsin variants in thyroid carcinoma cells. Biol Chem. 2010;391:923–35.PubMedPubMedCentralCrossRefGoogle Scholar
  135. Tertov VV, Orekhov AN. Metabolism of native and naturally occurring multiple modified low density lipoprotein in smooth muscle cells of human aortic intima. Exp Mol Pathol. 1997;64:127–45.PubMedCrossRefGoogle Scholar
  136. Tong B, Wan B, Wei Z, Wang T, Zhao P, Dou Y, Lv Z, Xia Y, Dai Y. Role of cathepsin B in regulating migration and invasion of fibroblast-like synoviocytes into inflamed tissue from patients with rheumatoid arthritis. Clin Exp Immunol. 2014;177:586–97.PubMedPubMedCentralCrossRefGoogle Scholar
  137. Tu C, Ortega-Cava CF, Chen G, Fernandes ND, Cavallo-Medved D, Sloane BF, Band V, Band H. Lysosomal cathepsin B participates in the podosome-mediated extracellular matrix degradation and invasion via secreted lysosomes in v-Src fibroblasts. Cancer Res. 2008;68:9147–56.PubMedPubMedCentralCrossRefGoogle Scholar
  138. Turk B. Targeting proteases: successes, failures and future prospects. Nat Rev Drug Discov. 2006;5:785–99.PubMedCrossRefGoogle Scholar
  139. Turk B, Turk V, Turk D. Structural and functional aspects of papain-like cysteine proteinases and their protein inhibitors. Biol Chem. 1997;378:141–50.PubMedPubMedCentralGoogle Scholar
  140. Turk D, Podobnik M, Kuhelj R, Dolinar M, Turk V. Crystal structures of human procathepsin B at 3.2 and 3.3 Angstroms resolution reveal an interaction motif between a papain-like cysteine protease and its propeptide. FEBS Lett. 1996;384:211–4.PubMedCrossRefGoogle Scholar
  141. Turk V, Bode W. The cystatins: protein inhibitors of cysteine proteinases. FEBS Lett. 1991;285:213–9.PubMedCrossRefGoogle Scholar
  142. Van Acker GJ. Co-localization hypothesis: a mechanism for the intrapancreatic activation of digestive enzymes during the early phases of acute pancreatitis. World J Gastroenterol. 2006;12:1985–90.PubMedPubMedCentralCrossRefGoogle Scholar
  143. Van Acker GJ, Saluja AK, Bhagat L, Singh VP, Song AM, Steer ML. Cathepsin B inhibition prevents trypsinogen activation and reduces pancreatitis severity. Am J Physiol Gastrointest Liver Physiol. 2002;283:G794–800.PubMedCrossRefGoogle Scholar
  144. van der Stappen JW, Williams AC, Maciewicz RA, Paraskeva C. Activation of cathepsin B, secreted by a colorectal cancer cell line requires low pH and is mediated by cathepsin D. Int J Cancer. 1996;67:547–54.PubMedCrossRefGoogle Scholar
  145. Wang Q, Zhong YJ, Yuan JP, Shao LH, Zhang J, Tang L, Liu SP, Hong YP, Firestone RA, Li Y. Targeting therapy of hepatocellular carcinoma with doxorubicin prodrug PDOX increases anti-metastatic effect and reduces toxicity: a preclinical study. J Transl Med. 2013;11:192.PubMedPubMedCentralCrossRefGoogle Scholar
  146. Weber E, Barbulescu E, Medek R, Reinheckel T, Sameni M, Anbalagan A, Moin K, Sloane BF. Cathepsin B-deficient mice as source of monoclonal anti-cathepsin B antibodies. Biol Chem. 2015;396:277–81.PubMedPubMedCentralCrossRefGoogle Scholar
  147. Weidle UH, Tiefenthaler G, Georges G. Proteases as activators for cytotoxic prodrugs in antitumor therapy. Cancer Genomics Proteomics. 2014;11:67–79.PubMedPubMedCentralGoogle Scholar
  148. Willstätter R, Bamann E. Über die Proteasen der Magenschleimhaut. Erste Abhandlung über die Enzymes der Leukocyten. Hoppe-Seyler’s Z Physiol Chem. 1929;180:127–43.CrossRefGoogle Scholar
  149. Withana NP, Ma X, McGuire HM, Verdoes M, van der Linden WA, Ofori LO, Zhang R, Li H, Sanman LE, Wei K, Yao S, Wu P, Li F, Huang H, Xu Z, Wolters PJ, Rosen GD, Collard HR, Zhu Z, Cheng Z, Bogyo M. Non-invasive Imaging of Idiopathic Pulmonary Fibrosis Using Cathepsin Protease Probes. Sci Rep. 2016;6:19755.PubMedPubMedCentralCrossRefGoogle Scholar
  150. Yamashita M, Konagaya S. A novel cysteine protease inhibitor of the egg of chum salmon, containing a cysteine-rich thyroglobulin-like motif. J Biol Chem. 1996;271:1282–4.PubMedCrossRefGoogle Scholar
  151. Yan S, Berquin IM, Troen BR, Sloane BF. Transcription of human cathepsin B is mediated by Sp1 and Ets family factors in glioma. DNA Cell Biol. 2000;19:79–91.PubMedCrossRefGoogle Scholar
  152. Yan S, Sloane BF. Molecular regulation of human cathepsin B: implication in pathologies. Biol Chem. 2003;384:845–54.PubMedPubMedCentralGoogle Scholar
  153. Yan S, Sloane BF. Isolation of a novel USF2 isoform: repressor of cathepsin B expression. Gene. 2004;337:199–206.PubMedCrossRefGoogle Scholar
  154. Yan Z, Deng X, Chen M, Xu Y, Ahram M, Sloane BF, Friedman E. Oncogenic c-Ki-ras but not oncogenic c-Ha-ras up-regulates CEA expression and disrupts basolateral polarity in colon epithelial cells. J Biol Chem. 1997;272:27902–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Dora Cavallo-Medved
    • 1
    • 2
  • Bonnie F. Sloane
    • 1
    • 3
  • Kamiar Moin
    • 1
    • 3
  1. 1.Department of PharmacologyWayne State UniversityDetroitUSA
  2. 2.Department of Biological SciencesUniversity of WindsorWindsorCanada
  3. 3.Barbara Ann Karmanos Cancer InstituteWayne State UniversityDetroitUSA