cathepsins

Summary

Summary: A group of lysosomal proteinases or endopeptidases found in aqueous extracts of a variety of animal tissues. They function optimally within an acidic pH range. The cathepsins occur as a variety of enzyme subtypes including SERINE PROTEASES; ASPARTIC PROTEINASES; and CYSTEINE PROTEASES.

Top Publications

  1. Guha S, Padh H. Cathepsins: fundamental effectors of endolysosomal proteolysis. Indian J Biochem Biophys. 2008;45:75-90 pubmed
    ..Endosomes contain significant levels of proteases like cathepsins and are sites of potent intracellular proteolysis...
  2. Gocheva V, Wang H, Gadea B, Shree T, Hunter K, Garfall A, et al. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev. 2010;24:241-55 pubmed publisher
    ..We further show that tumor-associated macrophage (TAM)-supplied cathepsins B and S are critical for promoting pancreatic tumor growth, angiogenesis, and invasion in vivo, and markedly ..
  3. Staun Ram E, Miller A. Cathepsins (S and B) and their inhibitor Cystatin C in immune cells: modulation by interferon-? and role played in cell migration. J Neuroimmunol. 2011;232:200-6 pubmed publisher
    ..These findings support further studies in the importance of Cathepsins and Cystatins in immunomodulation.
  4. Le Q, Min H, Xia H, Fukuoka Y, Katunuma N, Schwartz L. Promiscuous processing of human alphabeta-protryptases by cathepsins L, B, and C. J Immunol. 2011;186:7136-43 pubmed publisher
    ..Thus, CTSL and CTSB are capable of directly processing both ?- and ?-protryptases from human mast cells to their mature enzymatically active products. ..
  5. Česen M, Pegan K, Spes A, Turk B. Lysosomal pathways to cell death and their therapeutic applications. Exp Cell Res. 2012;318:1245-51 pubmed publisher
    ..Among the hydrolases, the cathepsins, a group of proteases enclosed in the lysosomes, have a major role...
  6. Cattaruzza F, Lyo V, Jones E, Pham D, Hawkins J, Kirkwood K, et al. Cathepsin S is activated during colitis and causes visceral hyperalgesia by a PAR2-dependent mechanism in mice. Gastroenterology. 2011;141:1864-74.e1-3 pubmed publisher
    ..We investigated the activation and function of cysteine cathepsins (Cat) in colitis...
  7. Gorodkiewicz E, Regulska E. SPR imaging biosensor for aspartyl cathepsins: sensor development and application for biological material. Protein Pept Lett. 2010;17:1148-54 pubmed
    ..In order to demonstrate the sensor's potential, Cat E was determined in human red blood cells, Cat D in human saliva, as well as total concentration of Cat D and Cat E in human nasal polyps. ..
  8. Repnik U, Stoka V, Turk V, Turk B. Lysosomes and lysosomal cathepsins in cell death. Biochim Biophys Acta. 2012;1824:22-33 pubmed publisher
    Lysosomes are the key degradative compartments of the cell. Lysosomal cathepsins, which are enclosed in the lysosomes, help to maintain the homeostasis of the cell's metabolism by participating in the degradation of heterophagic and ..
  9. Gormley J, Hegarty S, O Grady A, Stevenson M, Burden R, Barrett H, et al. The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study. Br J Cancer. 2011;105:1487-94 pubmed publisher
    ..02) and OS (P=0.04) in a multivariate model adjusted for known prognostic markers. These results signify that CatS may be an important prognostic biomarker and predictive of response to adjuvant FU/FA in CRC. ..

More Information

Publications62

  1. Peri P, Nuutila K, Vuorinen T, Saukko P, Hukkanen V. Cathepsins are involved in virus-induced cell death in ICP4 and Us3 deletion mutant herpes simplex virus type 1-infected monocytic cells. J Gen Virol. 2011;92:173-80 pubmed publisher
    ..This indicates that cathepsins B, L and S may act as cell-death mediators in d120-infected monocytic cells...
  2. Ahn S, Choi J, Rengaraj D, Seo H, Lim W, Han J, et al. Increased expression of cysteine cathepsins in ovarian tissue from chickens with ovarian cancer. Reprod Biol Endocrinol. 2010;8:100 pubmed publisher
    Cysteine cathepsins (CTSs) are involved in the degradation and remodeling of the extracellular matrix and are associated with cell transformation, differentiation, motility, and adhesion...
  3. Chen B, Platt M. Multiplex zymography captures stage-specific activity profiles of cathepsins K, L, and S in human breast, lung, and cervical cancer. J Transl Med. 2011;9:109 pubmed publisher
    b>Cathepsins K, L, and S are cysteine proteases upregulated in cancer and proteolyze extracellular matrix to facilitate metastasis, but difficulty distinguishing specific cathepsin activity in complex tissue extracts confounds scientific ..
  4. Clark A, Malcangio M. Microglial signalling mechanisms: Cathepsin S and Fractalkine. Exp Neurol. 2012;234:283-92 pubmed publisher
    ..Thus, impairment of the CatS/FKN signalling pair constitutes a novel therapeutic approach for the treatment of chronic pain. ..
  5. Biniossek M, Nägler D, Becker Pauly C, Schilling O. Proteomic identification of protease cleavage sites characterizes prime and non-prime specificity of cysteine cathepsins B, L, and S. J Proteome Res. 2011;10:5363-73 pubmed publisher
    Cysteine cathepsins mediate proteome homeostasis and have pivotal functions in diseases such as cancer...
  6. Naudin C, Joulin Giet A, Couetdic G, Plesiat P, Szymanska A, Gorna E, et al. Human cysteine cathepsins are not reliable markers of infection by Pseudomonas aeruginosa in cystic fibrosis. PLoS ONE. 2011;6:e25577 pubmed publisher
    Cysteine cathepsins have emerged as new players in inflammatory lung disorders. Their activities are dramatically increased in the sputum of cystic fibrosis (CF) patients, suggesting that they are involved in the pathophysiology of CF...
  7. Cheng X, Huang Z, Kuzuya M, Okumura K, Murohara T. Cysteine protease cathepsins in atherosclerosis-based vascular disease and its complications. Hypertension. 2011;58:978-86 pubmed publisher
    ..and serine proteases participate in these pathological events, the discovery of cysteine protease cathepsins, such as cathepsins K, S, L, and B, and cystatin C, and their tissue distribution has suggested that at least ..
  8. Hitchman R, Possee R, Siaterli E, Richards K, Clayton A, Bird L, et al. Improved expression of secreted and membrane-targeted proteins in insect cells. Biotechnol Appl Biochem. 2010;56:85-93 pubmed publisher
    ..In summary, we have conclusively demonstrated the importance of this deletion vector for the high-level production of recombinant proteins. ..
  9. Lafarge J, Naour N, Clement K, Guerre Millo M. Cathepsins and cystatin C in atherosclerosis and obesity. Biochimie. 2010;92:1580-6 pubmed publisher
    ..The importance of cathepsins was brought to light in this context...
  10. Norbury L, Hung A, Beckham S, Pike R, Spithill T, Craik C, et al. Analysis of Fasciola cathepsin L5 by S2 subsite substitutions and determination of the P1-P4 specificity reveals an unusual preference. Biochimie. 2012;94:1119-27 pubmed publisher
    ..Finally, the P(1)-P(4) specificity of Fasciola cathepsin L5 was determined and, unexpectedly, aspartic acid was shown to be well accepted at P(2,) which is unique amongst Fasciola cathepsins examined to date.
  11. Tjäderhane L, Nascimento F, Breschi L, Mazzoni A, Tersariol I, Geraldeli S, et al. Optimizing dentin bond durability: control of collagen degradation by matrix metalloproteinases and cysteine cathepsins. Dent Mater. 2013;29:116-35 pubmed publisher
    ..Dentin contains collagenolytic enzymes, matrix metalloproteinases (MMPs) and cysteine cathepsins, which are responsible for the hydrolytic degradation of collagen matrix in the bonded interface...
  12. Tersariol I, Geraldeli S, Minciotti C, Nascimento F, Pääkkönen V, Martins M, et al. Cysteine cathepsins in human dentin-pulp complex. J Endod. 2010;36:475-81 pubmed publisher
    ..We hypothesized that odontoblasts express other collagen-degrading enzymes such as cysteine cathepsins, and their activity would be present in dentin, because odontoblasts are known to express at least cathepsin D...
  13. Sasaki T, Kuzuya M, Nakamura K, Cheng X, Hayashi T, Song H, et al. AT1 blockade attenuates atherosclerotic plaque destabilization accompanied by the suppression of cathepsin S activity in apoE-deficient mice. Atherosclerosis. 2010;210:430-7 pubmed publisher
    Although it has been suggested that the renin-angiotensin (RA) system and cathepsins contribute to the development and vulnerability of atherosclerotic plaque, the interaction of the RA system and cathepsins is unclear...
  14. Yin J, Howe J, Tan K. Staurosporine-induced programmed cell death in Blastocystis occurs independently of caspases and cathepsins and is augmented by calpain inhibition. Microbiology. 2010;156:1284-93 pubmed publisher
    ..Interestingly, the apoptosis phenotype was insensitive to inhibitors of caspases and cathepsins B and L, while calpain-specific inhibitors augmented the STS-induced apoptosis response...
  15. Baugh M, Black D, Westwood P, Kinghorn E, McGregor K, Bruin J, et al. Therapeutic dosing of an orally active, selective cathepsin S inhibitor suppresses disease in models of autoimmunity. J Autoimmun. 2011;36:201-9 pubmed publisher
    ..CSI-75 caused a significant reduction in disease score in both disease models, indicating a promising role for CatS inhibitors in the area of therapeutic treatments for autoimmune diseases. ..
  16. Fan F, Nie S, Dammer E, Duong D, Pan D, Ping L, et al. Protein profiling of active cysteine cathepsins in living cells using an activity-based probe containing a cell-penetrating peptide. J Proteome Res. 2012;11:5763-72 pubmed publisher
    ..of a novel trifunctional cell-permeable activity-based probe (TCpABP) for proteomic profiling of active cysteine cathepsins in living cells...
  17. Dev A, Byrne S, Verma R, Ashton Rickardt P, Wojchowski D. Erythropoietin-directed erythropoiesis depends on serpin inhibition of erythroblast lysosomal cathepsins. J Exp Med. 2013;210:225-32 pubmed publisher
    ..Overall, we define an unexpected EPO action mode via an EPOR-Spi2A serpin-cathepsin axis in maturing erythroblasts, with lysosomal cathepsins as novel therapeutic targets.
  18. Wiens M, Wang X, Schröder H, Kolb U, Schlossmacher U, Ushijima H, et al. The role of biosilica in the osteoprotegerin/RANKL ratio in human osteoblast-like cells. Biomaterials. 2010;31:7716-25 pubmed publisher
    ..g. maturation of pre-osteoclasts and activation of osteoclasts). Hence, the data obtained in the present study reveal the considerable biomedical potential of biosilica for treatment and prophylaxis of osteoporotic disorders. ..
  19. Naour N, Rouault C, Fellahi S, Lavoie M, Poitou C, Keophiphath M, et al. Cathepsins in human obesity: changes in energy balance predominantly affect cathepsin s in adipose tissue and in circulation. J Clin Endocrinol Metab. 2010;95:1861-8 pubmed publisher
    Recent studies in humans and mice suggest the implication of the cysteine proteases cathepsins S, L, and K in vascular and metabolic complications of obesity...
  20. Fontanesi L, Speroni C, Buttazzoni L, Scotti E, Costa L, Davoli R, et al. Association between cathepsin L (CTSL) and cathepsin S (CTSS) polymorphisms and meat production and carcass traits in Italian Large White pigs. Meat Sci. 2010;85:331-8 pubmed publisher
    ..Overall these results, together with those previously reported for other genes of this family, suggest that cathepsin genes play a role in defining economically important traits in pigs...
  21. Jobs E, Riserus U, Ingelsson E, Helmersson J, Nerpin E, Jobs M, et al. Serum cathepsin S is associated with serum C-reactive protein and interleukin-6 independently of obesity in elderly men. J Clin Endocrinol Metab. 2010;95:4460-4 pubmed publisher
    ..These results provide additional evidence for the interplay between cathepsin S and inflammatory activity and suggest that this association is present also in normal-weight individuals in the community. ..
  22. Clark A, Wodarski R, Guida F, Sasso O, Malcangio M. Cathepsin S release from primary cultured microglia is regulated by the P2X7 receptor. Glia. 2010;58:1710-26 pubmed publisher
  23. Martin S, Moffitt K, McDowell A, Greenan C, Bright Thomas R, Jones A, et al. Association of airway cathepsin B and S with inflammation in cystic fibrosis. Pediatr Pulmonol. 2010;45:860-8 pubmed publisher
    ..This data indicates that cathepsin B and S may have important roles in the pathophysiology of CF lung disease and could have potential as markers of inflammation in future studies. ..
  24. Yamashima T. Reconsider Alzheimer's disease by the 'calpain-cathepsin hypothesis'--a perspective review. Prog Neurobiol. 2013;105:1-23 pubmed publisher
    ..this causes lysosomal permeabilization and/or rupture with the resultant release of the cell degradation enzyme, cathepsins (calpain-cathepsin hypothesis)...
  25. Rai A, Perry C. Facile fabrication of uniform silica films with tunable physical properties using silicatein protein from sponges. Langmuir. 2010;26:4152-9 pubmed publisher
    ..This simple route to prepare silica films of controlled physical properties could have potential application in membrane fabrication, biomedical devices, biosensors, and next generation electronic components. ..
  26. Phipps Yonas H, Semik V, HASTINGS K. GILT expression in B cells diminishes cathepsin S steady-state protein expression and activity. Eur J Immunol. 2013;43:65-74 pubmed publisher
  27. Jobs E, Ingelsson E, Riserus U, Nerpin E, Jobs M, Sundstrom J, et al. Association between serum cathepsin S and mortality in older adults. JAMA. 2011;306:1113-21 pubmed publisher
    ..Additional research is needed to delineate the role of cathepsin S and whether its measurement might have clinical utility. ..
  28. Vitner E, Dekel H, Zigdon H, Shachar T, Farfel Becker T, Eilam R, et al. Altered expression and distribution of cathepsins in neuronopathic forms of Gaucher disease and in other sphingolipidoses. Hum Mol Genet. 2010;19:3583-90 pubmed publisher
    ..We now show significant changes in the levels and in the distribution of cathepsins in the brain of this mouse model...
  29. El Hage T, Lorin S, Decottignies P, Djavaheri Mergny M, Authier F. Proteolysis of Pseudomonas exotoxin A within hepatic endosomes by cathepsins B and D produces fragments displaying in vitro ADP-ribosylating and apoptotic effects. FEBS J. 2010;277:3735-49 pubmed publisher
    ..lysate and pure proteases, the ETA-degrading activity was attributed to the luminal species of endosomal acidic cathepsins B and D, with the major cleavages generated in vitro occurring mainly within domain III of ETA-A...
  30. Gole B, Huszthy P, Popovic M, Jeruc J, Ardebili Y, Bjerkvig R, et al. The regulation of cysteine cathepsins and cystatins in human gliomas. Int J Cancer. 2012;131:1779-89 pubmed publisher
    Cysteine cathepsins play an important role in shaping the highly infiltrative growth pattern of human gliomas...
  31. Lopez Castejon G, Theaker J, Pelegrin P, Clifton A, Braddock M, Surprenant A. P2X(7) receptor-mediated release of cathepsins from macrophages is a cytokine-independent mechanism potentially involved in joint diseases. J Immunol. 2010;185:2611-9 pubmed publisher
    ..b>Cathepsins released into the medium were effective to degrade collagen extracellular matrix...
  32. Pozgan U, Caglic D, Rozman B, Nagase H, Turk V, Turk B. Expression and activity profiling of selected cysteine cathepsins and matrix metalloproteinases in synovial fluids from patients with rheumatoid arthritis and osteoarthritis. Biol Chem. 2010;391:571-9 pubmed publisher
    Cysteine cathepsins and matrix metalloproteases are considered to play important roles in the development of arthritic diseases. Their accumulation in synovial fluid of primarily rheumatoid arthritis patients is also well documented...
  33. Konjar S, Yin F, Bogyo M, Turk B, Kopitar Jerala N. Increased nucleolar localization of SpiA3G in classically but not alternatively activated macrophages. FEBS Lett. 2010;584:2201-6 pubmed publisher
    ..Since only pro-inflammatory, but not anti-inflammatory stimuli induce increased nucleolar localization of SpiA3G, we propose that SpiA3g translocation into the nucleolus is important in host defense against pathogens. ..
  34. Magister S, Obermajer N, Mirković B, Svajger U, Renko M, Softić A, et al. Regulation of cathepsins S and L by cystatin F during maturation of dendritic cells. Eur J Cell Biol. 2012;91:391-401 pubmed publisher
    In dendritic cells (DCs) cysteine cathepsins play a key role in antigen processing, invariant chain (Ii) cleavage and regulation of cell adhesion after maturation stimuli...
  35. Chen K, Chang W, Cheung C, Lin C, Huang C, Yang Y, et al. Targeting cathepsin S induces tumor cell autophagy via the EGFR-ERK signaling pathway. Cancer Lett. 2012;317:89-98 pubmed publisher
    ..In conclusion, the current study reveals that cathepsin S plays an important role in the regulation of cell autophagy through interference with the EGFR-ERK/MAPK-signaling pathway. ..
  36. Kolwijck E, Kos J, Obermajer N, Span P, Thomas C, Massuger L, et al. The balance between extracellular cathepsins and cystatin C is of importance for ovarian cancer. Eur J Clin Invest. 2010;40:591-9 pubmed publisher
    ..Extracellular release of lysosomal proteases (cathepsins) and their inhibitors has been associated with the development and progression of several types of cancer...
  37. Johansson A, Appelqvist H, Nilsson C, Kågedal K, Roberg K, Ollinger K. Regulation of apoptosis-associated lysosomal membrane permeabilization. Apoptosis. 2010;15:527-40 pubmed publisher
    ..membrane permeabilization (LMP) occurs in response to a large variety of cell death stimuli causing release of cathepsins from the lysosomal lumen into the cytosol where they participate in apoptosis signaling...
  38. Stoeckle C, Quecke P, Rückrich T, Burster T, Reich M, Weber E, et al. Cathepsin S dominates autoantigen processing in human thymic dendritic cells. J Autoimmun. 2012;38:332-43 pubmed publisher
    ..The peptides presented on MHC II molecules are generated by lysosomal proteases such as the cathepsins. At the same time, lysosomal proteases will also destroy other potential T cell epitopes from self-antigens...
  39. Conus S, Simon H. Cathepsins and their involvement in immune responses. Swiss Med Wkly. 2010;140:w13042 pubmed publisher
    ..Within the immune response, endo-lysosomal proteases play a key role. In this review we cover specific roles of cathepsins in innate and adaptive immunity, as well as their implication in the pathogenesis of several diseases.
  40. Ewald S, Engel A, Lee J, Wang M, Bogyo M, Barton G. Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase. J Exp Med. 2011;208:643-51 pubmed publisher
    ..This dual requirement for AEP and cathepsins is observed in all cell types that we have analyzed, including mouse macrophages and dendritic cells...
  41. Veillard F, Saidi A, Burden R, Scott C, Gillet L, Lecaille F, et al. Cysteine cathepsins S and L modulate anti-angiogenic activities of human endostatin. J Biol Chem. 2011;286:37158-67 pubmed publisher
    ..Here, we propose that cysteine cathepsins are involved in both the liberation and activation of bioactive endostatin fragments, thus regulating their anti-..
  42. Côté M, MISASI J, Ren T, Bruchez A, Lee K, Filone C, et al. Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection. Nature. 2011;477:344-8 pubmed publisher
    ..Thus, NPC1 is essential for EboV entry and a target for antiviral therapy. ..
  43. Creasy B, McCoy K. Cytokines regulate cysteine cathepsins during TLR responses. Cell Immunol. 2011;267:56-66 pubmed publisher
    ..Cysteine cathepsins (Cat) B, L and S, which are endosomal and lysosomal proteases, participate in numerous physiological systems and ..
  44. Tedelind S, Poliakova K, Valeta A, Hunegnaw R, Yemanaberhan E, Heldin N, et al. Nuclear cysteine cathepsin variants in thyroid carcinoma cells. Biol Chem. 2010;391:923-35 pubmed publisher
    ..As deduced from co-localization studies and in vitro degradation assays, we suggest that nuclear variants of cathepsins are involved in the development of thyroid malignancies through modification of DNA-associated proteins.
  45. Kreuzaler P, Staniszewska A, Li W, Omidvar N, Kedjouar B, Turkson J, et al. Stat3 controls lysosomal-mediated cell death in vivo. Nat Cell Biol. 2011;13:303-9 pubmed publisher
    ..We anticipate that these findings will be of major importance in the design of treatments for cancers such as breast, colon and liver, where cathepsins and Stat3 are commonly overexpressed and/or hyperactivated respectively.
  46. Hook V, Funkelstein L, Wegrzyn J, Bark S, Kindy M, Hook G. Cysteine Cathepsins in the secretory vesicle produce active peptides: Cathepsin L generates peptide neurotransmitters and cathepsin B produces beta-amyloid of Alzheimer's disease. Biochim Biophys Acta. 2012;1824:89-104 pubmed publisher
    ..These secretory vesicle functions of cathepsins L and B for production of biologically active peptides contrast with the well-known role of cathepsin proteases ..
  47. Sulpizio S, Franceschini N, Piattelli A, Di Sebastiano P, Innocenti P, Selvaggi F. Cathepsins and pancreatic cancer: the 2012 update. Pancreatology. 2012;12:395-401 pubmed publisher
    ..b>Cathepsins are proteolytic enzymes and represent potential therapeutic targets in human tumors...
  48. Dou Z, Carruthers V. Cathepsin proteases in Toxoplasma gondii. Adv Exp Med Biol. 2011;712:49-61 pubmed publisher
    ..Recent genetic, biochemical and structural studies reveal that cathepsins function in microneme and rhoptry protein maturation, host cell invasion, replication and nutrient acquisition...
  49. Schechter I, Ziv E. Cathepsins S, B and L with aminopeptidases display ?-secretase activity associated with the pathogenesis of Alzheimer's disease. Biol Chem. 2011;392:555-69 pubmed publisher
    ..6 m(-1) s(-1)). Therefore we searched for additional ?-secretases and identified three cathepsins that split the WT ?-site much faster...
  50. Pietschmann P, Foger Samwald U, Sipos W, Rauner M. The role of cathepsins in osteoimmunology. Crit Rev Eukaryot Gene Expr. 2013;23:11-26 pubmed
    b>Cathepsins are proteases comprising two small groups of serine and aspartic cathepsins and a large group of lysosomal cysteine cathepsins...
  51. Löser R, Bergmann R, Frizler M, Mosch B, Dombrowski L, Kuchar M, et al. Synthesis and radiopharmacological characterisation of a fluorine-18-labelled azadipeptide nitrile as a potential PET tracer for in?vivo imaging of cysteine cathepsins. ChemMedChem. 2013;8:1330-44 pubmed publisher
    ..positron emission tomography (PET) tracer development owing to its high affinity for the oncologically relevant cathepsins L, S, K and B...
  52. Laskar A, Ghosh M, Khattak S, Li W, Yuan X. Degradation of superparamagnetic iron oxide nanoparticle-induced ferritin by lysosomal cathepsins and related immune response. Nanomedicine (Lond). 2012;7:705-17 pubmed publisher
    ..Desferrioxamine prevents induction of both ferritin and cathepsin L by SPIONs. Inhibition of lysosomal cathepsins upregulates both endogenous- and SPION-induced ferritin...
  53. Zheng Y, Lai W, Wan M, Maibach H. Expression of cathepsins in human skin photoaging. Skin Pharmacol Physiol. 2011;24:10-21 pubmed publisher
    b>Cathepsins are involved in regulatory mechanisms in human skin, but their role in photoaged skin remains unknown. This study investigates the role of cathepsin B, D, K, and G in skin photoaging in vivo and in vitro...