Ctsl

Summary

Gene Symbol: Ctsl
Description: cathepsin L
Alias: 1190035F06Rik, CatL, Ctsl1, MEP, nkt, cathepsin L1, Cat L, major excreted protein, p39 cysteine proteinase
Species: mouse
Products:     Ctsl

Top Publications

  1. Lennon Dumenil A, Roberts R, Valentijn K, Driessen C, Overkleeft H, Erickson A, et al. The p41 isoform of invariant chain is a chaperone for cathepsin L. EMBO J. 2001;20:4055-64 pubmed
    ..class II-associated invariant chain (Ii) contains a 65 aa segment that binds to the active site of cathepsin L (CatL), a lysosomal cysteine protease involved in MHC class II-restricted antigen presentation...
  2. Honey K, Nakagawa T, Peters C, Rudensky A. Cathepsin L regulates CD4+ T cell selection independently of its effect on invariant chain: a role in the generation of positively selecting peptide ligands. J Exp Med. 2002;195:1349-58 pubmed
    ..Thus, we propose a novel role for cathepsin L in regulating positive selection by generating the major histocompatibility complex class II bound peptide ligands presented by cortical thymic epithelial cells. ..
  3. Tobin D, Foitzik K, Reinheckel T, Mecklenburg L, Botchkarev V, Peters C, et al. The lysosomal protease cathepsin L is an important regulator of keratinocyte and melanocyte differentiation during hair follicle morphogenesis and cycling. Am J Pathol. 2002;160:1807-21 pubmed
    We have previously shown that the ubiquitously expressed lysosomal cysteine protease, cathepsin L (CTSL), is essential for skin and hair follicle homeostasis...
  4. Yang M, Zhang Y, Pan J, Sun J, Liu J, Libby P, et al. Cathepsin L activity controls adipogenesis and glucose tolerance. Nat Cell Biol. 2007;9:970-7 pubmed
    Cysteine proteases play an important part in human pathobiology. This report shows the participation of cathepsin L (CatL) in adipogenesis and glucose intolerance...
  5. Reinheckel T, Hagemann S, Dollwet Mack S, Martinez E, Lohmüller T, Zlatkovic G, et al. The lysosomal cysteine protease cathepsin L regulates keratinocyte proliferation by control of growth factor recycling. J Cell Sci. 2005;118:3387-95 pubmed
    Mice deficient for cathepsin L (CTSL) show epidermal hyperplasia due to a hyperproliferation of basal keratinocytes. Here we show that the critical function of CTSL in the skin is keratinocyte specific...
  6. Chandran K, Sullivan N, Felbor U, Whelan S, Cunningham J. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science. 2005;308:1643-5 pubmed publisher
    ..cell lines, we identified an essential role for cathepsin B (CatB) and an accessory role for cathepsin L (CatL) in EboV GP-dependent entry...
  7. Sun M, Chen M, Liu Y, Fukuoka M, Zhou K, Li G, et al. Cathepsin-L contributes to cardiac repair and remodelling post-infarction. Cardiovasc Res. 2011;89:374-83 pubmed publisher
    Cathepsin-L (CTSL) is a member of the lysozomal cysteine protease family, which participates in remodelling of various tissues. Herein, we sought to examine the potential regulation of CTSL in cardiac remodelling post-infarction...
  8. Yasothornsrikul S, Greenbaum D, Medzihradszky K, Toneff T, Bundey R, Miller R, et al. Cathepsin L in secretory vesicles functions as a prohormone-processing enzyme for production of the enkephalin peptide neurotransmitter. Proc Natl Acad Sci U S A. 2003;100:9590-5 pubmed
    ..These findings indicate a previously uncharacterized biological role for secretory vesicle cathepsin L in the production of [Met]enkephalin, an endogenous peptide neurotransmitter. ..
  9. Maehr R, Mintern J, Herman A, Lennon Dumenil A, Mathis D, Benoist C, et al. Cathepsin L is essential for onset of autoimmune diabetes in NOD mice. J Clin Invest. 2005;115:2934-43 pubmed
    ..influence the outcome of a CD4+ T cell-dependent autoimmune response, we generated mice that lack cathepsin L (Cat L) on the autoimmune diabetes-prone NOD inbred background...

More Information

Publications85

  1. Funkelstein L, Toneff T, Mosier C, Hwang S, Beuschlein F, Lichtenauer U, et al. Major role of cathepsin L for producing the peptide hormones ACTH, beta-endorphin, and alpha-MSH, illustrated by protease gene knockout and expression. J Biol Chem. 2008;283:35652-9 pubmed publisher
    ..These findings demonstrate a prominent role for cathepsin L in the production of ACTH, beta-endorphin, and alpha-MSH peptide hormones in the regulated secretory pathway. ..
  2. Koike M, Shibata M, Waguri S, Yoshimura K, Tanida I, Kominami E, et al. Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroid-lipofuscinoses (Batten disease). Am J Pathol. 2005;167:1713-28 pubmed
    ..These data strongly argue for a major involvement of autophagy in the pathogenesis of Batten disease/lysosomal storage disorders. ..
  3. Shirahama Noda K, Yamamoto A, Sugihara K, Hashimoto N, Asano M, Nishimura M, et al. Biosynthetic processing of cathepsins and lysosomal degradation are abolished in asparaginyl endopeptidase-deficient mice. J Biol Chem. 2003;278:33194-9 pubmed
    ..Thus, the AEP deficiency caused the accumulation of macromolecules in the lysosomes, highlighting a pivotal role of AEP in the endosomal/lysosomal degradation system. ..
  4. Fiebiger E, Maehr R, Villadangos J, Weber E, Erickson A, Bikoff E, et al. Invariant chain controls the activity of extracellular cathepsin L. J Exp Med. 2002;196:1263-9 pubmed
    ..of major histocompatibility complex class II-associated invariant chain (Ii) binds to the active site of CatL and permits the maintenance of a pool of mature enzyme in endosomal compartments of macro-phages and dendritic ..
  5. Honey K, Benlagha K, Beers C, Forbush K, Teyton L, Kleijmeer M, et al. Thymocyte expression of cathepsin L is essential for NKT cell development. Nat Immunol. 2002;3:1069-74 pubmed
    ..We show that mice lacking the endosomal protease cathepsin L (catL) have greatly reduced numbers of V(alpha)14(+)NK1.1(+) T cells...
  6. Nakagawa T, Roth W, Wong P, Nelson A, Farr A, Deussing J, et al. Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus. Science. 1998;280:450-3 pubmed
    ..The identification of a protease involved in class II presentation in a tissue-specific manner suggests a potential means of manipulating CD4+ T cell responsiveness in vivo. ..
  7. Spira D, Stypmann J, Tobin D, Petermann I, Mayer C, Hagemann S, et al. Cell type-specific functions of the lysosomal protease cathepsin L in the heart. J Biol Chem. 2007;282:37045-52 pubmed
    Deficiency of the lysosomal cysteine protease cathepsin L (Ctsl) in mice results in a phenotype affecting multiple tissues, including thymus, epidermis, and hair follicles, and in the heart develops as a progressive dilated cardiomyopathy ..
  8. Ebert D, Deussing J, Peters C, Dermody T. Cathepsin L and cathepsin B mediate reovirus disassembly in murine fibroblast cells. J Biol Chem. 2002;277:24609-17 pubmed
    ..Moreover, these findings suggest that specific endocytic proteases can determine host cell susceptibility to infection by intracellular pathogens...
  9. Benavides F, Giordano M, Fiette L, Bueno Brunialti A, Martin Palenzuela N, Vanzulli S, et al. Nackt (nkt), a new hair loss mutation of the mouse with associated CD4 deficiency. Immunogenetics. 1999;49:413-9 pubmed
    A spontaneous recessive mutation named nackt (symbol: nkt) affecting hair growth and T-cell development was discovered in a moderately inbred stock of mice...
  10. 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. ..
  11. Hsieh C, deRoos P, Honey K, Beers C, Rudensky A. A role for cathepsin L and cathepsin S in peptide generation for MHC class II presentation. J Immunol. 2002;168:2618-25 pubmed
    ..This result suggests that these cysteinal proteases participate in Ag processing and generate qualitative and quantitative differences in the peptide repertoires displayed by MHC class II molecules. ..
  12. Tang Q, Cai J, Shen D, Bian Z, Yan L, Wang Y, et al. Lysosomal cysteine peptidase cathepsin L protects against cardiac hypertrophy through blocking AKT/GSK3beta signaling. J Mol Med (Berl). 2009;87:249-60 pubmed publisher
    The lysosomal cysteine peptidase cathepsin L (CTSL) is an important lysosomal proteinase involved in a variety of cellular functions including intracellular protein turnover, epidermal homeostasis, and hair development...
  13. Funkelstein L, Toneff T, Hwang S, Reinheckel T, Peters C, Hook V. Cathepsin L participates in the production of neuropeptide Y in secretory vesicles, demonstrated by protease gene knockout and expression. J Neurochem. 2008;106:384-91 pubmed publisher
    ..These studies illustrate the novel biological role of cathepsin L in the production of NPY, a peptide neurotransmitter, and neuroendocrine hormone. ..
  14. Roth W, Deussing J, Botchkarev V, Pauly Evers M, Saftig P, Hafner A, et al. Cathepsin L deficiency as molecular defect of furless: hyperproliferation of keratinocytes and pertubation of hair follicle cycling. FASEB J. 2000;14:2075-86 pubmed
    ..Cathepsin L (CTSL) is a ubiquitously expressed major representative of the papain-like family of cysteine proteinases...
  15. Stypmann J, Gläser K, Roth W, Tobin D, Petermann I, Matthias R, et al. Dilated cardiomyopathy in mice deficient for the lysosomal cysteine peptidase cathepsin L. Proc Natl Acad Sci U S A. 2002;99:6234-9 pubmed
    ..Here, we report that the lysosomal cysteine peptidase cathepsin L (CTSL) is critical for cardiac morphology and function...
  16. Lombardi G, Burzyn D, Mundiñano J, Berguer P, Bekinschtein P, Costa H, et al. Cathepsin-L influences the expression of extracellular matrix in lymphoid organs and plays a role in the regulation of thymic output and of peripheral T cell number. J Immunol. 2005;174:7022-32 pubmed
    Nackt mice, which are deficient in cathepsin-L (CTSL), show an early impairment during positive selection in the context of class II MHC molecules and as a consequence, the percentage and absolute number of CD4(+) thymocytes are ..
  17. Urbich C, Heeschen C, Aicher A, Sasaki K, Bruhl T, Farhadi M, et al. Cathepsin L is required for endothelial progenitor cell-induced neovascularization. Nat Med. 2005;11:206-13 pubmed
    ..We concluded that CathL has a critical role in the integration of circulating EPC into ischemic tissue and is required for EPC-mediated neovascularization. ..
  18. Shi G, Bryant R, Riese R, Verhelst S, Driessen C, Li Z, et al. Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages. J Exp Med. 2000;191:1177-86 pubmed
    ..These experiments show that cathepsin F, in a subset of antigen presenting cells (APCs), can efficiently degrade Ii. Different APCs can thus use distinct proteases to mediate MHC class II maturation and peptide loading. ..
  19. Benavides F, Venables A, Poetschke Klug H, Glasscock E, Rudensky A, Gomez M, et al. The CD4 T cell-deficient mouse mutation nackt (nkt) involves a deletion in the cathepsin L (CtsI) gene. Immunogenetics. 2001;53:233-42 pubmed
    ..of the mutant phenotype by demonstrating that the nkt mutation represents a 118-bp deletion of the cathepsin L (Ctsl) gene which is required for degradation of the invariant chain, a critical chaperone for major histocompatibility ..
  20. Dennemärker J, Lohmüller T, Mayerle J, Tacke M, Lerch M, Coussens L, et al. Deficiency for the cysteine protease cathepsin L promotes tumor progression in mouse epidermis. Oncogene. 2010;29:1611-21 pubmed publisher
    To define a functional role for the endosomal/lysosomal cysteine protease cathepsin L (Ctsl) during squamous carcinogenesis, we generated mice harboring a constitutive Ctsl deficiency in addition to epithelial expression of the human ..
  21. Felbor U, Kessler B, Mothes W, Goebel H, Ploegh H, Bronson R, et al. Neuronal loss and brain atrophy in mice lacking cathepsins B and L. Proc Natl Acad Sci U S A. 2002;99:7883-8 pubmed
    ..Our data demonstrate a pivotal role for cathepsins B and L in maintenance of the central nervous system. ..
  22. Hsing L, Kirk E, McMillen T, Hsiao S, Caldwell M, Houston B, et al. Roles for cathepsins S, L, and B in insulitis and diabetes in the NOD mouse. J Autoimmun. 2010;34:96-104 pubmed publisher
    ..00001). NODs lacking cathepsin L (Ctsl-/-) are completely protected from IDDM, as originally shown by others...
  23. Burke M, Hutter D, Reshamwala R, Knepper J. Cathepsin L plays an active role in involution of the mouse mammary gland. Dev Dyn. 2003;227:315-22 pubmed
    ..These data suggest that cathepsin L plays a regulatory role early in the process of mammary gland involution. ..
  24. Petermann I, Mayer C, Stypmann J, Biniossek M, Tobin D, Engelen M, et al. Lysosomal, cytoskeletal, and metabolic alterations in cardiomyopathy of cathepsin L knockout mice. FASEB J. 2006;20:1266-8 pubmed
    ..Mice deficient for the lysosomal cysteine protease cathepsin L (CTSL) develop a late onset dilated cardiomyopathy (DCM) that is characterized by cardiac chamber dilation, fibrosis, and ..
  25. Maehr R, Hang H, Mintern J, Kim Y, Cuvillier A, Nishimura M, et al. Asparagine endopeptidase is not essential for class II MHC antigen presentation but is required for processing of cathepsin L in mice. J Immunol. 2005;174:7066-74 pubmed
    ..Despite this, the numbers of CD4 and NK T cells are normal, showing that the single-chain form of Cat L is sufficient for its function in vivo...
  26. Benavides F, Starost M, Flores M, Gimenez Conti I, Guenet J, Conti C. Impaired hair follicle morphogenesis and cycling with abnormal epidermal differentiation in nackt mice, a cathepsin L-deficient mutation. Am J Pathol. 2002;161:693-703 pubmed
    ..Also, we recently reported that nkt (now Ctsl(nkt)) comprises a deletion in the cathepsin L (Ctsl) gene...
  27. Nepal R, Vesosky B, Turner J, Bryant P. DM, but not cathepsin L, is required to control an aerosol infection with Mycobacterium tuberculosis. J Leukoc Biol. 2008;84:1011-8 pubmed publisher
    ..Moreover, despite impaired thymic selection in Cat L(-/-) and DM(-/-) mice, MTB-specific CD4(+) T cells were elicited only in the former...
  28. Mihelic M, Dobersek A, Guncar G, Turk D. Inhibitory fragment from the p41 form of invariant chain can regulate activity of cysteine cathepsins in antigen presentation. J Biol Chem. 2008;283:14453-60 pubmed publisher
    ..These findings suggest that regulation of the proteolytic activity of most of the cysteine cathepsins by the p41 fragment is an important and widespread control mechanism of antigen presentation. ..
  29. Khalikova T, Korolenko T, Il nitskaia S. [The lysosomal cathepsins B, L and D in development of murine experimental leukemias]. Biomed Khim. 2009;55:621-34 pubmed
    ..Determination of the activity of cysteine and aspartic proteases can be used for evaluation of cancer diseases malignancy, their sensitivity for chemotherapy and efficiency of treatment. ..
  30. Wilson S, Peters C, Saftig P, Bromme D. Cathepsin K activity-dependent regulation of osteoclast actin ring formation and bone resorption. J Biol Chem. 2009;284:2584-92 pubmed publisher
  31. Sugita S, Horie S, Nakamura O, Maruyama K, Takase H, Usui Y, et al. Acquisition of T regulatory function in cathepsin L-inhibited T cells by eye-derived CTLA-2alpha during inflammatory conditions. J Immunol. 2009;183:5013-22 pubmed publisher
    ..In both EAU models, there was significant suppression of the ocular inflammation. These results indicate that RPE secretes CTLA-2alpha, thereby enabling the bystander T cells to be converted into Treg cells via TGF-beta promotion. ..
  32. Minokadeh A, Funkelstein L, Toneff T, Hwang S, Beinfeld M, Reinheckel T, et al. Cathepsin L participates in dynorphin production in brain cortex, illustrated by protease gene knockout and expression. Mol Cell Neurosci. 2010;43:98-107 pubmed publisher
    ..Overall, these results demonstrate a prominent role for cathepsin L, jointly with PC1/3 and PC2, for production of dynorphins in brain. ..
  33. Chauhan S, Popescu N, Ray D, Fleischmann R, Gottesman M, Troen B. Cloning, genomic organization, and chromosomal localization of human cathepsin L. J Biol Chem. 1993;268:1039-45 pubmed
  34. 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. ..
  35. Marzi A, Reinheckel T, Feldmann H. Cathepsin B & L are not required for ebola virus replication. PLoS Negl Trop Dis. 2012;6:e1923 pubmed publisher
    ..Later in this pathway endosomal acidification activates the cysteine proteases Cathepsin B and L (CatB, CatL), which have been shown to cleave ZEBOV-GP leading to subsequent exposure of the putative receptor-binding and ..
  36. Tholen M, Hillebrand L, Tholen S, Sedelmeier O, Arnold S, Reinheckel T. Out-of-frame start codons prevent translation of truncated nucleo-cytosolic cathepsin L in vivo. Nat Commun. 2014;5:4931 pubmed publisher
    ..In conclusion, the phenotypes of cathepsin L deficiency can be fully assigned to lack of canonically targeted cathepsin L, while the biogenesis and functionality of nucleo-cytosolic cathepsin L remain elusive. ..
  37. Koike M, Shibata M, Ohsawa Y, Nakanishi H, Koga T, Kametaka S, et al. Involvement of two different cell death pathways in retinal atrophy of cathepsin D-deficient mice. Mol Cell Neurosci. 2003;22:146-61 pubmed
  38. Sriraman V, Richards J. Cathepsin L gene expression and promoter activation in rodent granulosa cells. Endocrinology. 2004;145:582-91 pubmed
  39. 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. ..
  40. Stahl S, Reinders Y, Asan E, Mothes W, Conzelmann E, Sickmann A, et al. Proteomic analysis of cathepsin B- and L-deficient mouse brain lysosomes. Biochim Biophys Acta. 2007;1774:1237-46 pubmed
  41. Xu X, Greenland J, Gotts J, Matthay M, Caughey G. Cathepsin L Helps to Defend Mice from Infection with Influenza A. PLoS ONE. 2016;11:e0164501 pubmed publisher
    Host-derived proteases can augment or help to clear infections. This dichotomy is exemplified by cathepsin L (CTSL), which helps Hendra virus and SARS coronavirus to invade cells, but is essential for survival in mice with mycoplasma ..
  42. Mehanna S, Suzuki C, Shibata M, Sunabori T, Imanaka T, Araki K, et al. Cathepsin D in pancreatic acinar cells is implicated in cathepsin B and L degradation, but not in autophagic activity. Biochem Biophys Res Commun. 2016;469:405-11 pubmed publisher
    ..We therefore conclude that CD in pancreatic acinar cells is implicated in CB and CL degradation but not in autophagic activity. ..
  43. Tholen S, Biniossek M, Gansz M, Ahrens T, Schlimpert M, Kizhakkedathu J, et al. Double deficiency of cathepsins B and L results in massive secretome alterations and suggests a degradative cathepsin-MMP axis. Cell Mol Life Sci. 2014;71:899-916 pubmed publisher
    Endolysosomal cysteine cathepsins functionally cooperate. Cathepsin B (Ctsb) and L (Ctsl) double-knockout mice die 4 weeks after birth accompanied by (autophago-) lysosomal accumulations within neurons...
  44. Miller G, Matthews S, Reinheckel T, Fleming S, Watts C. Asparagine endopeptidase is required for normal kidney physiology and homeostasis. FASEB J. 2011;25:1606-17 pubmed publisher
    ..Thus, AEP is required for normal protein catabolism by PTCs, and its loss induces proliferative and other abnormalities in the murine kidney, at least in part through defective regulation of the EGF receptor. ..
  45. Lee J, Yu W, Kumar A, Lee S, Mohan P, Peterhoff C, et al. Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell. 2010;141:1146-58 pubmed publisher
    ..Defective lysosomal proteolysis represents a basis for pathogenic protein accumulations and neuronal cell death in AD and suggests previously unidentified therapeutic targets. ..
  46. Lombardi G, Burzyn D, Mundiñano J, Berguer P, Costa H, Goldman A, et al. Response to comment on "Cathepsin-L influences the expression of extracellular matrix in lymphoid organs and plays a role in the regulation of thymic output and of peripheral T cell number". J Immunol. 2006;176:5135-6 pubmed
  47. Allan E, Yates R. Redundancy between Cysteine Cathepsins in Murine Experimental Autoimmune Encephalomyelitis. PLoS ONE. 2015;10:e0128945 pubmed publisher
    ..This study demonstrates the functional redundancy between cathepsin B, S and L in EAE, and suggests that the inhibition of multiple cysteine cathepsins may be needed to modulate autoimmune disorders such as multiple sclerosis. ..
  48. Brindle N, Joyce J, Rostker F, Lawlor E, Swigart Brown L, Evan G, et al. Deficiency for the cysteine protease cathepsin L impairs Myc-induced tumorigenesis in a mouse model of pancreatic neuroendocrine cancer. PLoS ONE. 2015;10:e0120348 pubmed publisher
    ..Thus, genetic blockade of cathepsin L activity is inferred to retard Myc-driven tumor growth, encouraging the potential utility of pharmacological inhibitors of cysteine cathepsins in treating late stage tumors. ..
  49. Zhang Y, Spiess E, Groschup M, Burkle A. Up-regulation of cathepsin B and cathepsin L activities in scrapie-infected mouse Neuro2a cells. J Gen Virol. 2003;84:2279-83 pubmed
    ..We hypothesize that lysosomal proteases may be involved in a 'second autocatalytic loop' of PrP(Sc) formation, acting in concert with the well-known autocatalytic enhancement of PrP conversion in the presence of PrP(Sc). ..
  50. Walz M, Kellermann S, Bylaite M, Andrée B, Ruther U, Paus R, et al. Expression of the human Cathepsin L inhibitor hurpin in mice: skin alterations and increased carcinogenesis. Exp Dermatol. 2007;16:715-23 pubmed
    ..b>Cat L is involved in lysosomal protein degradation, hair follicle morphogenesis, epidermal differentiation and epitope ..
  51. Rocken C, Fändrich M, Stix B, Tannert A, Hortschansky P, Reinheckel T, et al. Cathepsin protease activity modulates amyloid load in extracerebral amyloidosis. J Pathol. 2006;210:478-87 pubmed
    ..CathL was identified as an amyloid-promoting and CathK as an amyloid-retarding cysteine protease. CathB may only modulate the primary structure of the amyloid peptide without affecting amyloid load. ..
  52. Tang C, Lee J, Galvez M, Robillard L, Mole S, Chapman H. Murine cathepsin F deficiency causes neuronal lipofuscinosis and late-onset neurological disease. Mol Cell Biol. 2006;26:2309-16 pubmed
    ..cat F is the only cysteine cathepsin whose inactivation alone causes a lysosomal storage defect and progressive neurological features in mice. The late onset suggests that this gene may be a candidate for adult-onset NCL. ..
  53. Timmons P, Rigby P, Poirier F. The murine seminiferous epithelial cycle is pre-figured in the Sertoli cells of the embryonic testis. Development. 2002;129:635-47 pubmed
  54. Grimm S, Horlacher M, Catalgol B, Hoehn A, Reinheckel T, Grune T. Cathepsins D and L reduce the toxicity of advanced glycation end products. Free Radic Biol Med. 2012;52:1011-23 pubmed publisher
    ..In summary we conclude that both cathepsins are required for a reduction in advanced glycation end product-induced cytotoxicity. ..
  55. Bhutani N, Piccirillo R, Hourez R, Venkatraman P, Goldberg A. Cathepsins L and Z are critical in degrading polyglutamine-containing proteins within lysosomes. J Biol Chem. 2012;287:17471-82 pubmed publisher
    ..g. mutant SOD1). Therefore, the activities of these two lysosomal cysteine proteases are important in host defense against toxic accumulation of polyQ proteins. ..
  56. Garsen M, Rops A, Dijkman H, Willemsen B, van Kuppevelt T, Russel F, et al. Cathepsin L is crucial for the development of early experimental diabetic nephropathy. Kidney Int. 2016;90:1012-1022 pubmed publisher
    ..Thus, cathepsin L is causally involved in the pathogenesis of experimental diabetic nephropathy. Most likely, cathepsin L-dependent heparanase activation is crucial for the development of albuminuria and renal damage. ..
  57. Shimada N, Ohno Matsui K, Iseki S, Koike M, Uchiyama Y, Wang J, et al. Cathepsin L in bone marrow-derived cells is required for retinal and choroidal neovascularization. Am J Pathol. 2010;176:2571-80 pubmed publisher
    ..These data indicate that cathepsin L expressed in endothelial progenitor cells plays a critical role in intraocular angiogenesis and suggest a potential therapeutic approach of targeting cathepsin L for neovascular ocular diseases. ..
  58. Abboud Jarrous G, Atzmon R, Peretz T, Palermo C, Gadea B, Joyce J, et al. Cathepsin L is responsible for processing and activation of proheparanase through multiple cleavages of a linker segment. J Biol Chem. 2008;283:18167-76 pubmed publisher
    ..The critical involvement of cathepsin L in proheparanase processing and activation offers new strategies for inhibiting the prometastatic, proangiogenic, and proinflammatory activities of heparanase. ..
  59. Okamoto T, Toyooka K, Minamikawa T. Identification of a membrane-associated cysteine protease with possible dual roles in the endoplasmic reticulum and protein storage vacuole. J Biol Chem. 2001;276:742-51 pubmed
    ..The protease was named membrane-associated cysteine protease, MCP. The possibility that a papain-type enzyme, MCP, exists as mature enzyme in both ER and protein storage vacuoles will be discussed. ..
  60. Samokhin A, Gauthier J, Percival M, Bromme D. Lack of cathepsin activities alter or prevent the development of lung granulomas in a mouse model of sarcoidosis. Respir Res. 2011;12:13 pubmed publisher
    ..Cathepsin K deficiency affected mostly the occurrence and composition of lung granulomas, whereas cathepsin L deficiency significantly reduced their number and cathepsin S inhibition prevented the formation of granulomas. ..
  61. Baer G, Ebert D, Chung C, Erickson A, Dermody T. Mutant cells selected during persistent reovirus infection do not express mature cathepsin L and do not support reovirus disassembly. J Virol. 1999;73:9532-43 pubmed
    ..These findings indicate that persistent reovirus infections select cellular mutations that affect the maturation of cathepsin L and suggest that alterations in the expression of lysosomal proteases can modulate viral cytopathicity. ..
  62. Steenhuis P, Froemming J, Reinheckel T, Storch S. Proteolytic cleavage of the disease-related lysosomal membrane glycoprotein CLN7. Biochim Biophys Acta. 2012;1822:1617-28 pubmed publisher
    ..Our findings suggest that CLN7 is inactivated by proteolytic cleavage and that enhanced CLN7 proteolysis caused by missense mutations in selected luminal loops is associated with disease. ..
  63. Alain T, Kim T, Lun X, Liacini A, Schiff L, Senger D, et al. Proteolytic disassembly is a critical determinant for reovirus oncolysis. Mol Ther. 2007;15:1512-21 pubmed
    ..Together, these results provide a model in which proteolytic disassembly of reovirus is a critical determinant of susceptibility to reovirus oncolysis...
  64. Ohrvik H, Logeman B, Turk B, Reinheckel T, Thiele D. Cathepsin Protease Controls Copper and Cisplatin Accumulation via Cleavage of the Ctr1 Metal-binding Ectodomain. J Biol Chem. 2016;291:13905-16 pubmed publisher
    ..These studies identify a new processing event and the key protease that cleaves the Ctr1 metal-binding ectodomain, which functions to regulate cellular Cu(+) and cisplatin acquisition. ..
  65. Sun M, Ouzounian M, de Couto G, Chen M, Yan R, Fukuoka M, et al. Cathepsin-L ameliorates cardiac hypertrophy through activation of the autophagy-lysosomal dependent protein processing pathways. J Am Heart Assoc. 2013;2:e000191 pubmed publisher
    ..These effects were partially rescued with CTSL1 replacement via adeno-associated virus-mediated gene transfer...
  66. Lennon Dumenil A, Bakker A, Maehr R, Fiebiger E, Overkleeft H, Rosemblatt M, et al. Analysis of protease activity in live antigen-presenting cells shows regulation of the phagosomal proteolytic contents during dendritic cell activation. J Exp Med. 2002;196:529-40 pubmed
    ..Phagosomal maturation is therefore a tightly regulated process that varies according to the type and differentiation stage of the phagocyte. ..
  67. Roy K, Maricic I, Khurana A, Smith T, Halder R, Kumar V. Involvement of secretory and endosomal compartments in presentation of an exogenous self-glycolipid to type II NKT cells. J Immunol. 2008;180:2942-50 pubmed
    Natural Killer T (NKT) cells recognize both self and foreign lipid Ags presented by CD1 molecules...
  68. Wright W, Smith L, Kerr C, Charron M. Mice that express enzymatically inactive cathepsin L exhibit abnormal spermatogenesis. Biol Reprod. 2003;68:680-7 pubmed
    ..This proenzyme prevents atrophy of seminiferous tubules and promotes the formation of preleptotene spermatocytes and the differentiation of these meiotic cells into pachytene spermatocytes. ..
  69. Cheon Y, DeMayo F, Bagchi M, Bagchi I. Induction of cytotoxic T-lymphocyte antigen-2beta, a cysteine protease inhibitor in decidua: a potential regulator of embryo implantation. J Biol Chem. 2004;279:10357-63 pubmed
    ..Collectively, our results support the hypothesis that expression of CTLA-2beta in the decidua may regulate implantation of the embryo by neutralizing the activities of one or more proteases generated by the proliferating trophoblast. ..
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    ..We investigated whether cathepsin L (CTSL) can also process trypsinogen to active trypsin and has a role in pancreatitis...
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    ..In humans, insulin-stimulated cathepsin L expression in skeletal muscle is impaired in diabetic but not in nondiabetic monozygotic twins, suggesting that the changes may be secondary to impaired glucose metabolism. ..
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    ..The striking roles of lysosomal enzymes in epidermis during lipid remodeling and desquamation may also reflect the observed high abundance of high mannose glycans. ..
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    ..Thus individual cysteine cathepsin genes make distinctive contributions to tumorigenesis. ..
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    ..DNA clones corresponding to 638 nucleotides of the messenger RNA encoding the major portion of murine major excreted protein have been isolated and sequenced...
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    ..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. ..
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    ..of cathepsin L in normal physiological processes was assessed using cathepsin L homozygous knockout mice (B6;129-Ctsl(tm1Alpk)). These mice were generated using gene targeting in embryonic stem cells...