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Gene Review

Cts7-ps  -  cathepsin 7, pseudogene

Mus musculus

Synonyms: Cts1, Cts1-ps
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Disease relevance of Cts7-ps

  • When mice were injected intravenously with the cathepsin reporter probe, intestinal adenomas became highly fluorescent indicative of high cathepsin B enzyme activity [1].
  • Using gene expression profiling, we identified cathepsin cysteine proteases as highly up-regulated genes in a mouse model of human lung adenocarcinoma [2].
  • This compound potently inhibited cathepsin activity in situ, in human osteoclasts (inhibitor concentration [IC]50 = 70 nM) as well as bone resorption mediated by human osteoclasts in vitro (IC50 = 29 nM) [3].
  • Cathepsin protease activity modulates amyloid load in extracerebral amyloidosis [4].
  • These data suggest that cathepsin-mediated cleavage could prime AAV capsids for subsequent nuclear uncoating, and indicate that analysis of additional genes recovered in our screen may help to further elucidate the mechanisms behind transduction by AAV8 and related serotypes.Molecular Therapy (2007) 15, 330-339. doi:10.1038/ [5].

High impact information on Cts7-ps

  • IL-6-mediated STAT3 activation decreased cystatin C level, an endogenous inhibitor of cathepsins, and enhanced cathepsin activities [6].
  • We show that the defect in positive selection in the cathepsin L-/- thymus is specific for CD4+ T cells that can be selected in a wild-type and provide evidence that the repertoire of T cells selected differs from that in wild-type mice, suggesting cortical thymic epithelial cells in cathepsin L knockout mice express an altered peptide repertoire [7].
  • Cathepsin (Cat) S and L are the major elastinolytic cysteine proteases in mouse macrophages [8].
  • We show that CTL and NK cells die within a few hours if they are triggered to degranulate in the presence of nontoxic thiol cathepsin protease inhibitors [9].
  • Immunolabeling demonstrated a rearrangement of the endocytic system and a redistribution of extracellularly located enzymes in thyroids of cathepsin-deficient mice [10].

Chemical compound and disease context of Cts7-ps


Biological context of Cts7-ps


Anatomical context of Cts7-ps

  • Although the absence of these proteases provoked a modest shift in the efficiency of presentation of some antigenic determinants, the overall capacity of Cat B-/- or Cat D-/- antigen-presenting cells was unaffected [14].
  • Certain tumor cell lines directly stimulate platelet activity, some by releasing platelet-aggregating material, a urea-extractable membrane component, others by release of cathepsin, and still others by undefined mechanisms [19].
  • Because an acidic pericellular pH has been shown to induce translocation of lysosomes in macrophages and fibroblasts, we evaluated the intracellular distribution of cathepsin B+ vesicles and secretion of cathepsin B in cell pairs incubated at slightly acidic pH [20].
  • Substrate gel electrophoresis showed an increase in giant cell cathepsin activity with enzyme profiles changing at the end of the invasive period [16].
  • Both the redistribution of cathepsin B+ vesicles toward the cell surface induced by acidic pH and the constitutive and acidic pH-induced secretion of active cathepsin B could be inhibited by microtubule poisons and stabilizers [20].

Associations of Cts7-ps with chemical compounds


Physical interactions of Cts7-ps


Regulatory relationships of Cts7-ps


Other interactions of Cts7-ps

  • Mixed lysates of L cells and LX cells lack activity of both cathepsin B and cathepsin L, suggesting the presence of an inhibitor of cathepsin function in LX cells [26].
  • Furthermore, cathepsin expression was similar to the expression of the macrophage marker macrosialin (CD68) although expression of cathepsins B, D, and L could be demonstrated in healthy C57BL/6 mice and in nonaffected vessel segments of atherosclerotic ApoE-/- mice [27].
  • Cycloheximide treatment of peritoneal macrophages inhibited the increase in cathepsin H mRNA levels induced by IFN-gamma, suggesting that the increase in cathepsin mRNA levels requires de novo protein synthesis [28].
  • Proinsulin/insulin is synthesized locally and prevents caspase- and cathepsin-mediated cell death in the embryonic mouse retina [29].
  • Treatment of cells in vivo with two cell permeant peptide fluoromethylketone inhibitors of caspase activity, Z-VAD-fmk and Z-DEVD-fmk, inhibited DX- and TG-induced apoptotic nuclear changes and maintained plasma membrane integrity, whereas the cathepsin inhibitor, Z-FA-fmk, and two calpain inhibitors failed to inhibit apoptosis [30].

Analytical, diagnostic and therapeutic context of Cts7-ps


  1. Detection of dysplastic intestinal adenomas using enzyme-sensing molecular beacons in mice. Marten, K., Bremer, C., Khazaie, K., Sameni, M., Sloane, B., Tung, C.H., Weissleder, R. Gastroenterology (2002) [Pubmed]
  2. Use of gene expression profiling to direct in vivo molecular imaging of lung cancer. Grimm, J., Kirsch, D.G., Windsor, S.D., Kim, C.F., Santiago, P.M., Ntziachristos, V., Jacks, T., Weissleder, R. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  3. Potent and selective inhibition of human cathepsin K leads to inhibition of bone resorption in vivo in a nonhuman primate. Stroup, G.B., Lark, M.W., Veber, D.F., Bhattacharyya, A., Blake, S., Dare, L.C., Erhard, K.F., Hoffman, S.J., James, I.E., Marquis, R.W., Ru, Y., Vasko-Moser, J.A., Smith, B.R., Tomaszek, T., Gowen, M. J. Bone Miner. Res. (2001) [Pubmed]
  4. Cathepsin protease activity modulates amyloid load in extracerebral amyloidosis. R??cken, C., F??ndrich, M., Stix, B., Tannert, A., Hortschansky, P., Reinheckel, T., Saftig, P., K??hne, T., Menard, R., Ancsin, J., B??hling, F. J. Pathol. (2006) [Pubmed]
  5. A Two-hybrid Screen Identifies Cathepsins B and L as Uncoating Factors for Adeno-associated Virus 2 and 8. Akache, B., Grimm, D., Shen, X., Fuess, S., Yant, S.R., Glazer, D.S., Park, J., Kay, M.A. Mol. Ther. (2007) [Pubmed]
  6. IL-6-STAT3 controls intracellular MHC class II alphabeta dimer level through cathepsin S activity in dendritic cells. Kitamura, H., Kamon, H., Sawa, S., Park, S.J., Katunuma, N., Ishihara, K., Murakami, M., Hirano, T. Immunity (2005) [Pubmed]
  7. Cathepsin L regulates CD4+ T cell selection independently of its effect on invariant chain: a role in the generation of positively selecting peptide ligands. Honey, K., Nakagawa, T., Peters, C., Rudensky, A. J. Exp. Med. (2002) [Pubmed]
  8. Invariant chain controls the activity of extracellular cathepsin L. Fiebiger, E., Maehr, R., Villadangos, J., Weber, E., Erickson, A., Bikoff, E., Ploegh, H.L., Lennon-Duménil, A.M. J. Exp. Med. (2002) [Pubmed]
  9. Surface cathepsin B protects cytotoxic lymphocytes from self-destruction after degranulation. Balaji, K.N., Schaschke, N., Machleidt, W., Catalfamo, M., Henkart, P.A. J. Exp. Med. (2002) [Pubmed]
  10. Thyroid functions of mouse cathepsins B, K, and L. Friedrichs, B., Tepel, C., Reinheckel, T., Deussing, J., von Figura, K., Herzog, V., Peters, C., Saftig, P., Brix, K. J. Clin. Invest. (2003) [Pubmed]
  11. Antitumor agents. XXXIV: Mechanism of action of bruceoside A and brusatol on nucleic acid metabolism of P-388 lymphocytic leukemia cells. Hall, I.H., Lee, K.H., Eigebaly, S.A., Imakura, Y., Sumida, Y., Wu, R.Y. Journal of pharmaceutical sciences. (1979) [Pubmed]
  12. Cathepsins B, L and D in inflammatory bowel disease macrophages and potential therapeutic effects of cathepsin inhibition in vivo. Menzel, K., Hausmann, M., Obermeier, F., Schreiter, K., Dunger, N., Bataille, F., Falk, W., Scholmerich, J., Herfarth, H., Rogler, G. Clin. Exp. Immunol. (2006) [Pubmed]
  13. Exposure to hypoxia, glucose starvation and acidosis: effect on invasive capacity of murine tumor cells and correlation with cathepsin (L + B) secretion. Cuvier, C., Jang, A., Hill, R.P. Clin. Exp. Metastasis (1997) [Pubmed]
  14. Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation. Deussing, J., Roth, W., Saftig, P., Peters, C., Ploegh, H.L., Villadangos, J.A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  15. JNK2 mediates TNF-induced cell death in mouse embryonic fibroblasts via regulation of both caspase and cathepsin protease pathways. Dietrich, N., Thastrup, J., Holmberg, C., Gyrd-Hansen, M., Fehrenbacher, N., Lademann, U., Lerdrup, M., Herdegen, T., Jäättelä, M., Kallunki, T. Cell Death Differ. (2004) [Pubmed]
  16. The expression and function of cystatin C and cathepsin B and cathepsin L during mouse embryo implantation and placentation. Afonso, S., Romagnano, L., Babiarz, B. Development (1997) [Pubmed]
  17. Macrophage apoptosis in response to high intracellular burden of Mycobacterium tuberculosis is mediated by a novel caspase-independent pathway. Lee, J., Remold, H.G., Ieong, M.H., Kornfeld, H. J. Immunol. (2006) [Pubmed]
  18. Gallium arsenide modulates proteolytic cathepsin activities and antigen processing by macrophages. Lewis, T.A., Hartmann, C.B., McCoy, K.L. J. Immunol. (1998) [Pubmed]
  19. Potential role of platelets in the pathogenesis of tumor metastasis. Mehta, P. Blood (1984) [Pubmed]
  20. Pericellular pH affects distribution and secretion of cathepsin B in malignant cells. Rozhin, J., Sameni, M., Ziegler, G., Sloane, B.F. Cancer Res. (1994) [Pubmed]
  21. Calpains play a role in insulin secretion and action. Sreenan, S.K., Zhou, Y.P., Otani, K., Hansen, P.A., Currie, K.P., Pan, C.Y., Lee, J.P., Ostrega, D.M., Pugh, W., Horikawa, Y., Cox, N.J., Hanis, C.L., Burant, C.F., Fox, A.P., Bell, G.I., Polonsky, K.S. Diabetes (2001) [Pubmed]
  22. Cathepsin G, and not the asparagine-specific endoprotease, controls the processing of myelin basic protein in lysosomes from human B lymphocytes. Burster, T., Beck, A., Tolosa, E., Marin-Esteban, V., Rötzschke, O., Falk, K., Lautwein, A., Reich, M., Brandenburg, J., Schwarz, G., Wiendl, H., Melms, A., Lehmann, R., Stevanovic, S., Kalbacher, H., Driessen, C. J. Immunol. (2004) [Pubmed]
  23. Preclinical evaluation of cathepsin-degradable peptide linkers for radioimmunoconjugates. DeNardo, G.L., DeNardo, S.J., Peterson, J.J., Miers, L.A., Lam, K.S., Hartmann-Siantar, C., Lamborn, K.R. Clin. Cancer Res. (2003) [Pubmed]
  24. Cathepsin S regulates the expression of cathepsin L and the turnover of gamma-interferon-inducible lysosomal thiol reductase in B lymphocytes. Honey, K., Duff, M., Beers, C., Brissette, W.H., Elliott, E.A., Peters, C., Maric, M., Cresswell, P., Rudensky, A. J. Biol. Chem. (2001) [Pubmed]
  25. RANK ligand and interferon gamma differentially regulate cathepsin gene expression in pre-osteoclastic cells. Pang, M., Martinez, A.F., Jacobs, J., Balkan, W., Troen, B.R. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  26. Cathepsin B Is Inhibited in Mutant Cells Selected during Persistent Reovirus Infection. Ebert, D.H., Kopecky-Bromberg, S.A., Dermody, T.S. J. Biol. Chem. (2004) [Pubmed]
  27. Differential expression of cysteine and aspartic proteases during progression of atherosclerosis in apolipoprotein E-deficient mice. Jormsjö, S., Wuttge, D.M., Sirsjö, A., Whatling, C., Hamsten, A., Stemme, S., Eriksson, P. Am. J. Pathol. (2002) [Pubmed]
  28. IFN-gamma increases cathepsin H mRNA levels in mouse macrophages. Lafuse, W.P., Brown, D., Castle, L., Zwilling, B.S. J. Leukoc. Biol. (1995) [Pubmed]
  29. Proinsulin/insulin is synthesized locally and prevents caspase- and cathepsin-mediated cell death in the embryonic mouse retina. Valenciano, A.I., Corrochano, S., de Pablo, F., de la Villa, P., de la Rosa, E.J. J. Neurochem. (2006) [Pubmed]
  30. Apoptosis induction by the glucocorticoid hormone dexamethasone and the calcium-ATPase inhibitor thapsigargin involves Bc1-2 regulated caspase activation. McColl, K.S., He, H., Zhong, H., Whitacre, C.M., Berger, N.A., Distelhorst, C.W. Mol. Cell. Endocrinol. (1998) [Pubmed]
  31. Subcellular localization and targeting of cathepsin E. Finley, E.M., Kornfeld, S. J. Biol. Chem. (1994) [Pubmed]
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