Gene Symbol: Ctsc
Description: cathepsin C
Alias: AI047818, CatC, DPP1, DPPI, dipeptidyl peptidase 1, cathepsin J, dipeptidyl peptidase I, dipeptidyl transferase
Species: mouse
Products:     Ctsc

Top Publications

  1. Rao N, Rao G, Hoidal J. Human dipeptidyl-peptidase I. Gene characterization, localization, and expression. J Biol Chem. 1997;272:10260-5 pubmed
    ..The results provide initial insights into the molecular basis for the regulation of human dipeptidyl-peptidase I. ..
  2. McGuire M, Lipsky P, Thiele D. Cloning and characterization of the cDNA encoding mouse dipeptidyl peptidase I (cathepsin C). Biochim Biophys Acta. 1997;1351:267-73 pubmed
    The mouse dipeptidyl peptidase I cDNA has been cloned and sequenced and patterns of DPPI mRNA expression in various tissues characterized...
  3. Pham C, Ley T. Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo. Proc Natl Acad Sci U S A. 1999;96:8627-32 pubmed
    b>Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease that has been implicated in the processing of granzymes, which are neutral serine proteases exclusively expressed in the granules of activated cytotoxic lymphocytes...
  4. Wolters P, Pham C, Muilenburg D, Ley T, Caughey G. Dipeptidyl peptidase I is essential for activation of mast cell chymases, but not tryptases, in mice. J Biol Chem. 2001;276:18551-6 pubmed
    b>Dipeptidyl peptidase I (DPPI) is the sole activator in vivo of several granule-associated serine proteases of cytotoxic lymphocytes. In vitro, DPPI also activates mast cell chymases and tryptases...
  5. Mallen St Clair J, Pham C, Villalta S, Caughey G, Wolters P. Mast cell dipeptidyl peptidase I mediates survival from sepsis. J Clin Invest. 2004;113:628-34 pubmed
    Sepsis is a common, life-threatening disease for which there is little treatment. The cysteine protease dipeptidyl peptidase I (DPPI) activates granule-associated serine proteases, several of which play important roles in host responses ..
  6. Hu Y, Pham C. Dipeptidyl peptidase I regulates the development of collagen-induced arthritis. Arthritis Rheum. 2005;52:2553-8 pubmed
    To examine the role of dipeptidyl peptidase I (DPPI), a widely expressed lysosomal cysteine protease, in the development of collagen-induced arthritis (CIA) in mice...
  7. Paris A, Strukelj B, Pungercar J, Renko M, Dolenc I, Turk V. Molecular cloning and sequence analysis of human preprocathepsin C. FEBS Lett. 1995;369:326-30 pubmed
    ..5% identity. A multiple alignment of the deduced cathepsin C sequence of 233 residues which, by analogy to other cystein proteinases, corresponds to the mature protein, confirms that human cathepsin C belongs to the papain superfamily. ..
  8. Soehnlein O, Zernecke A, Eriksson E, Rothfuchs A, PHAM C, Herwald H, et al. Neutrophil secretion products pave the way for inflammatory monocytes. Blood. 2008;112:1461-71 pubmed publisher
    ..This cellular cross-talk functionally results in enhanced cytokine levels and increased bacterial clearance, thus boosting the early immune response. ..
  9. Akk A, Simmons P, Chan H, Agapov E, Holtzman M, Grayson M, et al. Dipeptidyl peptidase I-dependent neutrophil recruitment modulates the inflammatory response to Sendai virus infection. J Immunol. 2008;180:3535-42 pubmed
    ..In this study, we show that the absence of dipeptidyl peptidase I (DPPI), a lysosomal cysteine protease found in neutrophils, dampens the acute inflammatory response and ..

More Information


  1. 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
    ..Together, these data establish IL-4 as an important regulator, and cathepsin proteases as critical mediators, of the cancer-promoting functions of TAMs. ..
  2. Gurung P, Burton A, Kanneganti T. NLRP3 inflammasome plays a redundant role with caspase 8 to promote IL-1?-mediated osteomyelitis. Proc Natl Acad Sci U S A. 2016;113:4452-7 pubmed publisher
    ..In conclusion, our studies have uncovered the combined actions of the NLRP3 inflammasome and caspase 8 leading to IL-1? maturation and the directionality of IL-1? in driving disease inPstpip2(cmo)mice. ..
  3. Hamon Y, Legowska M, Hervé V, Dallet Choisy S, Marchand Adam S, Vanderlynden L, et al. Neutrophilic Cathepsin C Is Maturated by a Multistep Proteolytic Process and Secreted by Activated Cells during Inflammatory Lung Diseases. J Biol Chem. 2016;291:8486-99 pubmed publisher
    The cysteine protease cathepsin C (CatC) activates granule-associated proinflammatory serine proteases in hematopoietic precursor cells...
  4. Herías V, Biessen E, Beckers C, Delsing D, Liao M, Daemen M, et al. Leukocyte cathepsin C deficiency attenuates atherosclerotic lesion progression by selective tuning of innate and adaptive immune responses. Arterioscler Thromb Vasc Biol. 2015;35:79-86 pubmed publisher
    The protein degrading activity of cathepsin C (CatC), combined with its role in leukocyte granule activation, suggests a contribution of this cystein protease in atherosclerosis...
  5. Vidal E, Tortosa R, Marco P, Fondevila D, Rabanal R, Torres J, et al. Late stage cathepsin C, CXCL13 and Ki-67 overexpression correlate with regional neuropathology in a BSE transgenic murine model. J Comp Pathol. 2013;148:22-32 pubmed publisher
    ..These findings suggest that these proteins are involved in the mechanisms leading to the establishment of transmissible spongiform encephalopathy. ..
  6. Tye C, Pham C, Simmer J, Bartlett J. DPPI may activate KLK4 during enamel formation. J Dent Res. 2009;88:323-7 pubmed publisher
    ..KLK4 is secreted as an inactive zymogen (pro-KLK4), and identification of its activator remains elusive. Dipeptidyl peptidase I (DPPI) is a cysteine aminopeptidase that can activate several serine proteases...
  7. Pagano M, Bartoli M, Ennis T, Mao D, Simmons P, Thompson R, et al. Critical role of dipeptidyl peptidase I in neutrophil recruitment during the development of experimental abdominal aortic aneurysms. Proc Natl Acad Sci U S A. 2007;104:2855-60 pubmed
    b>Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease critical for the activation of granule-associated serine proteases, including neutrophil elastase, cathepsin G, and proteinase 3...
  8. Matsui K, Yuyama N, Akaiwa M, Yoshida N, Maeda M, Sugita Y, et al. Identification of an alternative splicing variant of cathepsin C/dipeptidyl-peptidase I. Gene. 2002;293:1-7 pubmed
    ..These results indicate that the variant may play a role in regulating the biological activities of cathepsin C, involved in the pathogenesis of bronchial asthma. ..
  9. Sevilla L, Nachat R, Groot K, Klement J, Uitto J, Djian P, et al. Mice deficient in involucrin, envoplakin, and periplakin have a defective epidermal barrier. J Cell Biol. 2007;179:1599-612 pubmed publisher
    ..Thus, combined loss of the cornified envelope proteins not only impairs the epidermal barrier, but also changes the composition of T cell subpopulations in the skin. ..
  10. Kono H, Orlowski G, Patel Z, Rock K. The IL-1-dependent sterile inflammatory response has a substantial caspase-1-independent component that requires cathepsin C. J Immunol. 2012;189:3734-40 pubmed
  11. Liu W, Yan M, Liu Y, McLeish K, Coleman W, Rodgers G. Olfactomedin 4 inhibits cathepsin C-mediated protease activities, thereby modulating neutrophil killing of Staphylococcus aureus and Escherichia coli in mice. J Immunol. 2012;189:2460-7 pubmed publisher
    ..These results indicate that OLFM4 is an important negative regulator of neutrophil bactericidal activity by restricting cathepsin C activity and its downstream granule-associated serine proteases. ..
  12. Levesque J, Liu F, Simmons P, Betsuyaku T, Senior R, Pham C, et al. Characterization of hematopoietic progenitor mobilization in protease-deficient mice. Blood. 2004;104:65-72 pubmed
    ..HPC mobilization by G-CSF was normal in MMP-9-deficient mice, NE x CG-deficient mice, or mice lacking dipeptidyl peptidase I, an enzyme required for the functional activation of many hematopoietic serine proteases...
  13. Andoniou C, Fleming P, Sutton V, Trapani J, Degli Esposti M. Cathepsin C limits acute viral infection independently of NK cell and CD8+ T-cell cytolytic function. Immunol Cell Biol. 2011;89:540-8 pubmed publisher
    ..The activation of a number of serine proteases, including GzmA and B, is predominately mediated by cathepsin C (CatC). Deficiencies in CatC-null mice were therefore expected to replicate the defects observed in GzmAB-deficient mice...
  14. D Angelo M, Bird P, Peters C, Reinheckel T, Trapani J, Sutton V. Cathepsin H is an additional convertase of pro-granzyme B. J Biol Chem. 2010;285:20514-9 pubmed publisher
    ..as a zymogen (proGrB) and activated in cytotoxic granules by the lysosomal cysteine protease cathepsin C (CatC) which removes the N-terminal dipeptide Gly-Glu...
  15. Raymond W, Xu X, Nimishakavi S, Le C, McDonald D, Caughey G. Regulation of hepatocyte growth factor in mice with pneumonia by peptidases and trans-alveolar flux. PLoS ONE. 2015;10:e0125797 pubmed publisher
    ..Unexpectedly, pneumonia severity was similar in wild type and dipeptidylpeptidase I-deficient (Dppi-/-) mice lacking neutrophil serine protease activity...
  16. Hart T, Hart P, Michalec M, Zhang Y, Firatli E, Van Dyke T, et al. Haim-Munk syndrome and Papillon-Lefèvre syndrome are allelic mutations in cathepsin C. J Med Genet. 2000;37:88-94 pubmed
    ..We also report a mutation of the same exon 6 CTSC codon (2126C-->T) in a Turkish family with classical PLS...
  17. Sutton V, Waterhouse N, Browne K, Sedelies K, Ciccone A, Anthony D, et al. Residual active granzyme B in cathepsin C-null lymphocytes is sufficient for perforin-dependent target cell apoptosis. J Cell Biol. 2007;176:425-33 pubmed
    ..Cathepsin C deficiency also results in considerably milder immune deficiency than perforin or granzyme A/B deficiency. ..
  18. Lilla J, Joshi R, Craik C, Werb Z. Active plasma kallikrein localizes to mast cells and regulates epithelial cell apoptosis, adipocyte differentiation, and stromal remodeling during mammary gland involution. J Biol Chem. 2009;284:13792-803 pubmed publisher
    ..Using biotinylated ecotin-PKal, we localized active PKal to connective tissue-type mast cells in the mammary gland. Taken together, these results implicate PKal as an effector of the plasminogen cascade during mammary development. ..
  19. Yan D, Wang H, Bowman R, Joyce J. STAT3 and STAT6 Signaling Pathways Synergize to Promote Cathepsin Secretion from Macrophages via IRE1? Activation. Cell Rep. 2016;16:2914-2927 pubmed publisher
    ..Together, these findings demonstrate that cytokine-activated STAT3 and STAT6 cooperate in macrophages to promote a secretory phenotype that enhances tumor progression in a cathepsin-dependent manner. ..
  20. Brojatsch J, Lima H, Palliser D, Jacobson L, Muehlbauer S, Furtado R, et al. Distinct cathepsins control necrotic cell death mediated by pyroptosis inducers and lysosome-destabilizing agents. Cell Cycle. 2015;14:964-72 pubmed publisher
    ..In contrast, cathepsins C and D were not required for pyroptotic cell death suggesting that distinct cathepsins control pyroptosis and lysosome-mediated necrosis. ..
  21. Nga B, Luziga C, Yamamoto M, Kusakabe K, Yamamoto Y. Identification and characterization of the interactive proteins with cytotoxic T-lymphocyte antigen-2α. Biosci Biotechnol Biochem. 2015;79:587-97 pubmed publisher
    ..A simple cell-based fluorescence assay revealed that CTLA-2α exhibited inhibitory activity toward cathepsin C in live cells, which indicated that CTLA-2α is a novel endogenous inhibitor of cathepsin C. ..
  22. Sanchez Martínez D, Krzywinska E, Rathore M, Saumet A, Cornillon A, López Royuela N, et al. All-trans retinoic acid (ATRA) induces miR-23a expression, decreases CTSC expression and granzyme B activity leading to impaired NK cell cytotoxicity. Int J Biochem Cell Biol. 2014;49:42-52 pubmed publisher
    ..our analysis by showing that activation down regulates miR-23a, which is a negative regulator of cathepsin C (CTSC) mRNA, a gene up regulated by all stimuli...
  23. Deu E, Chen I, Lauterwasser E, Valderramos J, Li H, Edgington L, et al. Ferrous iron-dependent drug delivery enables controlled and selective release of therapeutic agents in vivo. Proc Natl Acad Sci U S A. 2013;110:18244-9 pubmed publisher
    ..This approach may find useful application in parasitic infections and more broadly in any disease state characterized by aberrant production of reactive ferrous iron. ..
  24. Orlowski G, Sharma S, Colbert J, Bogyo M, Robertson S, Kataoka H, et al. Frontline Science: Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1β activation. J Leukoc Biol. 2017;102:7-17 pubmed publisher
    ..In support of this concept, we find that a broad-spectrum cathepsin inhibitor can suppress particle-induced IL-1-dependent peritonitis. ..
  25. Pottier N, Chupin C, Defamie V, Cardinaud B, Sutherland R, Rios G, et al. Relationships between early inflammatory response to bleomycin and sensitivity to lung fibrosis: a role for dipeptidyl-peptidase I and tissue inhibitor of metalloproteinase-3?. Am J Respir Crit Care Med. 2007;176:1098-107 pubmed
    ..The first corresponded to dipeptidyl-peptidase I (DPPI), a cysteine peptidase (also known as cathepsin C) essential for the activation of serine proteinases produced by ..
  26. Ruffell B, Affara N, Cottone L, Junankar S, Johansson M, DeNardo D, et al. Cathepsin C is a tissue-specific regulator of squamous carcinogenesis. Genes Dev. 2013;27:2086-98 pubmed publisher
    ..b>CtsC, on the other hand, while up-regulated during pancreatic islet carcinogenesis, lacks functional significance in ..
  27. Vethanayagam R, Almyroudis N, Grimm M, Lewandowski D, Pham C, Blackwell T, et al. Role of NADPH oxidase versus neutrophil proteases in antimicrobial host defense. PLoS ONE. 2011;6:e28149 pubmed publisher
    ..neutrophil elastase (NE)(-/-)×cathepsin G (CG)(-/-) mice and lysosomal cysteine protease cathepsin C/dipeptidyl peptidase I (DPPI)-deficient mice that are defective in neutrophil serine protease activation demonstrated no ..
  28. Zhang B, Zheng C, Zhu M, Tao J, Vasievich M, Baines A, et al. Mice deficient in LMAN1 exhibit FV and FVIII deficiencies and liver accumulation of ?1-antitrypsin. Blood. 2011;118:3384-91 pubmed publisher
  29. Gocheva V, Zeng W, Ke D, Klimstra D, Reinheckel T, Peters C, et al. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes Dev. 2006;20:543-56 pubmed
    ..Thus individual cysteine cathepsin genes make distinctive contributions to tumorigenesis. ..
  30. Regner M, Pavlinovic L, Koskinen A, Young N, Trapani J, Mullbacher A. Cutting edge: rapid and efficient in vivo cytotoxicity by cytotoxic T cells is independent of granzymes A and B. J Immunol. 2009;183:37-40 pubmed publisher
    ..Specific target cell elimination occurred with similar kinetics in both spleen and lymph nodes. Thus, neither gzmA nor gzmB are required for rapid and efficient in vivo cytotoxicity by Tc cells...
  31. Getachew Y, Stout Delgado H, Miller B, Thiele D. Granzyme C supports efficient CTL-mediated killing late in primary alloimmune responses. J Immunol. 2008;181:7810-7 pubmed
    ..In the present studies, CTL generated from mice deficient in dipeptidyl peptidase 1 (DPP1) were used to investigate the contribution of granzyme C to CTL killing of allogeneic target cells...
  32. Baumann M, Pham C, Benarafa C. SerpinB1 is critical for neutrophil survival through cell-autonomous inhibition of cathepsin G. Blood. 2013;121:3900-7, S1-6 pubmed publisher
    ..In conclusion, we have unveiled a new cytotoxic function for the serine protease CG and showed that serpinB1 is critical for maintaining PMN survival by antagonizing intracellular CG activity. ..
  33. Fan K, Wu X, Fan B, Li N, Lin Y, Yao Y, et al. Up-regulation of microglial cathepsin C expression and activity in lipopolysaccharide-induced neuroinflammation. J Neuroinflammation. 2012;9:96 pubmed publisher
  34. Sutherland R, Barry S, Olsen J, Salantes D, Caughey G, Wolters P. Dipeptidyl peptidase I controls survival from Klebsiella pneumoniae lung infection by processing surfactant protein D. Biochem Biophys Res Commun. 2014;450:818-823 pubmed publisher
    Prior work established that a deficiency in the cysteine protease dipeptidyl peptidase I (DPPI) improves survival following polymicrobial septic peritonitis...
  35. Winkler I, Sims N, Pettit A, Barbier V, Nowlan B, Helwani F, et al. Bone marrow macrophages maintain hematopoietic stem cell (HSC) niches and their depletion mobilizes HSCs. Blood. 2010;116:4815-28 pubmed publisher
    ..Together, these results establish that bone marrow macrophages are pivotal to maintain the endosteal HSC niche and that the loss of such macrophages leads to the egress of HSCs into the blood. ..
  36. Lilla J, Werb Z. Mast cells contribute to the stromal microenvironment in mammary gland branching morphogenesis. Dev Biol. 2010;337:124-33 pubmed publisher
    ..For mast cells to exert their effects on normal morphogenesis required activation of their serine proteases and degranulation. Our observations reveal a novel role for mast cells during normal pubertal development in the mammary gland. ..
  37. Pham C, Armstrong R, Zimonjic D, Popescu N, Payan D, Ley T. Molecular cloning, chromosomal localization, and expression of murine dipeptidyl peptidase I. J Biol Chem. 1997;272:10695-703 pubmed
    b>Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease that catalyzes the sequential removal of dipeptides from the amino termini of various protein substrates...
  38. Liang J, Li N, Zhang Y, Hou C, Yang X, Shimizu T, et al. Disinhibition of Cathepsin C Caused by Cystatin F Deficiency Aggravates the Demyelination in a Cuprizone Model. Front Mol Neurosci. 2016;9:152 pubmed publisher
    ..The findings gain further insight to function of Cat C in pathophysiology of MS, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future. ..
  39. Kim K, PHAM C, Sleat D, Lobel P. Dipeptidyl-peptidase I does not functionally compensate for the loss of tripeptidyl-peptidase I in the neurodegenerative disease late-infantile neuronal ceroid lipofuscinosis. Biochem J. 2008;415:225-32 pubmed publisher
    ..One such candidate is another lysosomal aminopeptidase, DPPI (dipeptidyl-peptidase I), which appears to have overlapping substrate specificity with TPPI and is expressed at ..
  40. Shimizu T, Wisessmith W, Li J, Abe M, Sakimura K, Chetsawang B, et al. The balance between cathepsin C and cystatin F controls remyelination in the brain of Plp1-overexpressing mouse, a chronic demyelinating disease model. Glia. 2017;65:917-930 pubmed publisher
    ..Here, we report the effects of manipulating the expression of CysF and cathepsin C (CatC), a key target of CysF, in a murine model of transgenic demyelinating disease, Plp4e/- ...