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Gene Review

Ctss  -  cathepsin S

Mus musculus

Synonyms: Cat S, Cathepsin S, Cats
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Disease relevance of Ctss


Psychiatry related information on Ctss


High impact information on Ctss

  • These events reflect a developmental regulation of invariant (Ii) chain cleavage, most likely by the cysteine protease cathepsin S [6].
  • Thus, the ratio of cystatin C to cathepsin S in developing DCs helps to determine the fate of newly synthesized MHC class II molecules [6].
  • In immature DCs, inefficient Ii chain cleavage due to low cathepsin S activity leads to the transport of class II-Ii chain complexes to lysosomes, while in mature DCs, elevated cathepsin S activity results in efficient delivery of class II alphabeta dimers to the plasma membrane [6].
  • Cathepsin S overexpression in DCs decreased intracellular MHCII alphabeta dimer, Ii, and H2-DM levels, LPS-mediated surface expression of MHCII and suppressed CD4(+) T cell activation [7].
  • IL-6-STAT3 controls intracellular MHC class II alphabeta dimer level through cathepsin S activity in dendritic cells [7].

Biological context of Ctss


Anatomical context of Ctss

  • Furthermore, we report that nonprofessional APC present a class II-bound endogenous peptide to naive CD4 T cells in vivo in a Cat S-dependent fashion [8].
  • Unexpectedly, we found that murine Cat S plays a critical role in invariant chain degradation in intestinal epithelial cells [8].
  • To examine this issue, we generated embryonic fibroblast lines that express CL, CS, or neither [13].
  • The cysteine endoprotease cathepsin S mediates degradation of the MHC class II invariant chain Ii in human and mouse antigen-presenting cells [1].
  • BACKGROUND: Cathepsin S is a member of the family of cysteine lysosomal proteases preferentially expressed in macrophages and microglia and is active after prolonged incubation in neutral pH [14].

Associations of Ctss with chemical compounds

  • Human atherosclerotic lesions overexpress the lysosomal cysteine protease cathepsin S (Cat S), one of the most potent mammalian elastases known [2].
  • Cathepsins F or K partially degraded lipid-free apoA-I and reduced its ability to induce cholesterol efflux, whereas cathepsin S totally degraded apoA-I, leading to complete loss of apoA-I cholesterol acceptor function [15].
  • Corpus luteum was the predominant location of cathepsin L. The distribution of cathepsin S resembled that of cathepsin L. The developing oocyte stained positive for all cathepsins [16].
  • Epoxy succinate peptide derivatives, CLIK-066, 088, 112, 121, 148, 181, 185 and 187, are typical specific inhibitors for cathepsin L. Aldehyde derivatives CLIK-060 and CLIK-164 showed specific inhibition against cathepsin S and cathepsin K, respectively [17].
  • It is shown that MGX (methylglyoxal), GO (glyoxal) and glycolaldehyde, but not hydroxyacetone and glucose, inhibit catB (cathepsin B), catL (cathepsin L) and catS (cathepsin S) activity in macrophage cell lysates, in a concentration-dependent manner [18].

Regulatory relationships of Ctss


Other interactions of Ctss


Analytical, diagnostic and therapeutic context of Ctss


  1. Cathepsin S inhibitor prevents autoantigen presentation and autoimmunity. Saegusa, K., Ishimaru, N., Yanagi, K., Arakaki, R., Ogawa, K., Saito, I., Katunuma, N., Hayashi, Y. J. Clin. Invest. (2002) [Pubmed]
  2. Deficiency of cathepsin S reduces atherosclerosis in LDL receptor-deficient mice. Sukhova, G.K., Zhang, Y., Pan, J.H., Wada, Y., Yamamoto, T., Naito, M., Kodama, T., Tsimikas, S., Witztum, J.L., Lu, M.L., Sakara, Y., Chin, M.T., Libby, P., Shi, G.P. J. Clin. Invest. (2003) [Pubmed]
  3. Important role of cathepsin S in generating peptides for TAP-independent MHC class I crosspresentation in vivo. Shen, L., Sigal, L.J., Boes, M., Rock, K.L. Immunity (2004) [Pubmed]
  4. Cathepsin S is required for murine autoimmune myasthenia gravis pathogenesis. Yang, H., Kala, M., Scott, B.G., Goluszko, E., Chapman, H.A., Christadoss, P. J. Immunol. (2005) [Pubmed]
  5. Microglial activation varies in different models of Creutzfeldt-Jakob disease. Baker, C.A., Lu, Z.Y., Zaitsev, I., Manuelidis, L. J. Virol. (1999) [Pubmed]
  6. Developmental regulation of invariant chain proteolysis controls MHC class II trafficking in mouse dendritic cells. Pierre, P., Mellman, I. Cell (1998) [Pubmed]
  7. 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]
  8. Cathepsin S controls MHC class II-mediated antigen presentation by epithelial cells in vivo. Beers, C., Burich, A., Kleijmeer, M.J., Griffith, J.M., Wong, P., Rudensky, A.Y. J. Immunol. (2005) [Pubmed]
  9. Changes in the spatial expression of genes with aging in the mouse RPE/choroid. Ogawa, T., Boylan, S.A., Oltjen, S.L., Hjelmeland, L.M. Mol. Vis. (2005) [Pubmed]
  10. Cathepsin S required for normal MHC class II peptide loading and germinal center development. Shi, G.P., Villadangos, J.A., Dranoff, G., Small, C., Gu, L., Haley, K.J., Riese, R., Ploegh, H.L., Chapman, H.A. Immunity (1999) [Pubmed]
  11. Dynamics of major histocompatibility complex class II compartments during B cell receptor-mediated cell activation. Lankar, D., Vincent-Schneider, H., Briken, V., Yokozeki, T., Raposo, G., Bonnerot, C. J. Exp. Med. (2002) [Pubmed]
  12. Analysis of protease activity in live antigen-presenting cells shows regulation of the phagosomal proteolytic contents during dendritic cell activation. Lennon-Duménil, A.M., Bakker, A.H., Maehr, R., Fiebiger, E., Overkleeft, H.S., Rosemblatt, M., Ploegh, H.L., Lagaudrière-Gesbert, C. J. Exp. Med. (2002) [Pubmed]
  13. A role for cathepsin L and cathepsin S in peptide generation for MHC class II presentation. Hsieh, C.S., deRoos, P., Honey, K., Beers, C., Rudensky, A.Y. J. Immunol. (2002) [Pubmed]
  14. Neurotrophic factors regulate cathepsin S in macrophages and microglia: A role in the degradation of myelin basic protein and amyloid beta peptide. Liuzzo, J.P., Petanceska, S.S., Devi, L.A. Mol. Med. (1999) [Pubmed]
  15. Cathepsins F and S block HDL3-induced cholesterol efflux from macrophage foam cells. Lindstedt, L., Lee, M., Oörni, K., Brömme, D., Kovanen, P.T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  16. Differential expression patterns of cathepsins B, H, K, L and S in the mouse ovary. Oksjoki, S., Söderström, M., Vuorio, E., Anttila, L. Mol. Hum. Reprod. (2001) [Pubmed]
  17. Study of the functional share of lysosomal cathepsins by the development of specific inhibitors. Katunuma, N., Matsui, A., Kakegawa, T., Murata, E., Asao, T., Ohba, Y. Adv. Enzyme Regul. (1999) [Pubmed]
  18. Evidence for inactivation of cysteine proteases by reactive carbonyls via glycation of active site thiols. Zeng, J., Dunlop, R.A., Rodgers, K.J., Davies, M.J. Biochem. J. (2006) [Pubmed]
  19. 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]
  20. PU.1 regulates cathepsin S expression in professional APCs. Wang, Y., Baron, R.M., Zhu, G., Joo, M., Christman, J.W., Silverman, E.S., Perrella, M.A., Riese, R.J., Cernadas, M. J. Immunol. (2006) [Pubmed]
  21. Identification of the increased expression of monocyte chemoattractant protein-1, cathepsin S, UPIX-1, and other genes in dystrophin-deficient mouse muscles by suppression subtractive hybridization. Fang, J., Shi, G.P., Vaghy, P.L. J. Cell. Biochem. (2000) [Pubmed]
  22. Identification and localization of retinal cystatin C. Wassélius, J., Håkansson, K., Johansson, K., Abrahamson, M., Ehinger, B. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  23. Cathepsins D, B, and L in transformed human breast epithelial cells. Lah, T.T., Calaf, G., Kalman, E., Shinde, B.G., Somers, R., Estrada, S., Salero, E., Russo, J., Daskal, I. Breast Cancer Res. Treat. (1996) [Pubmed]
  24. Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice. Nakagawa, T.Y., Brissette, W.H., Lira, P.D., Griffiths, R.J., Petrushova, N., Stock, J., McNeish, J.D., Eastman, S.E., Howard, E.D., Clarke, S.R., Rosloniec, E.F., Elliott, E.A., Rudensky, A.Y. Immunity (1999) [Pubmed]
  25. Human cathepsin S: chromosomal localization, gene structure, and tissue distribution. Shi, G.P., Webb, A.C., Foster, K.E., Knoll, J.H., Lemere, C.A., Munger, J.S., Chapman, H.A. J. Biol. Chem. (1994) [Pubmed]
  26. Reduced beta-amyloid production and increased inflammatory responses in presenilin conditional knock-out mice. Beglopoulos, V., Sun, X., Saura, C.A., Lemere, C.A., Kim, R.D., Shen, J. J. Biol. Chem. (2004) [Pubmed]
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