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Gene Review

Lox  -  lysyl oxidase

Mus musculus

Synonyms: AI893619, Lysyl oxidase, Protein-lysine 6-oxidase, Ras excision protein, Rrg, ...
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Disease relevance of Lox

  • Lox-targeted mice (LOX(-/-)) died soon after parturition, exhibiting cardiovascular instability with ruptured arterial aneurysms and diaphragmatic rupture [1].
  • Mouse Lox was recently shown to be crucial for development of the cardiovascular system because null mice died perinatally of aortic aneurysms and cardiovascular dysfunction [2].
  • Early effects of the dose were: prevention of the tremors and spasms seen in untreated mutants, raising to normal and near-normal of caeruloplasmin oxidase and lysyl oxidase activities and pigmentation of skin and fur [3].
  • To further understand the mechanism of cadmium toxicity, the mRNA expression, synthesis, post-translational processing, and catalytic activity of lysyl oxidase were examined in cadmium-resistant (CdR) cells and the cadmium-sensitive Swiss mouse 3T3 cells from which they were derived [4].
  • Both tools were used to examine the expression of the lysyl oxidase mRNAs and peptides, all within granulomas and cells extracted from infected liver [5].

High impact information on Lox

  • GFAP-Cre;Rb(LoxP/LoxP);p53(-/- or LoxP/LoxP) mice developed highly aggressive embryonal tumors of the cerebellum with typical features of medulloblastoma [6].
  • To investigate these opposite functions of DC, we generated a Cre/LoxP-based system that allows inducible antigen presentation by DC in vivo [7].
  • Therefore, we developed a LoxP/Cre-based conditional mutation approach to test the role of c-myc in mouse embryonic fibroblasts (MEFs) and mature B lymphocytes [8].
  • The mechanism of T cell lineage commitment remains controversial; to examine it we deleted the CD4-silencer element in the germ line of a mouse using a combination of gene targeting and Cre/LoxP-mediated recombination [9].
  • We here report that injected IL-10 protein is an efficient inhibitor of tumor metastasis in experimental (B16-F10) and spontaneous (M27 and Lox human melanoma) metastasis models in vivo at doses that do not have toxic effects on normal or cancer cells [10].

Chemical compound and disease context of Lox


Biological context of Lox


Anatomical context of Lox


Associations of Lox with chemical compounds

  • Autocrine pathways were blocked with suramin, a general inhibitor of growth factor receptor binding, and resulted in more than a 10-fold increase in lysyl oxidase expression and proenzyme production [14].
  • Treatment of ras-transformed cells with interferon-alpha with or without retinoic acid results in their persistent reversion to a non-transformed state that is dependent on the restoration of LO expression [17].
  • Transformation of revertant murine cells by 5-azacytidine results in rapid inhibition of lysyl oxidase expression [17].
  • Lysyl oxidase (LO), which catalyzes the oxidation of lysine residues, was previously shown to have anti-oncogenic activity on ras-transformed cells [18].
  • Notably, lung lysyl oxidase activity is markedly stimulated in rats exposed to cadmium vapors [4].

Enzymatic interactions of Lox


Regulatory relationships of Lox

  • Importantly, LO blocked membrane localization of Akt and PDK1 in Ras-transformed cells [18].
  • The full 2 kb murine LOX promoter was very active in 3T6-5 myofibroblast-like cells (MFLC) and vascular smooth muscle cells (SMC) and was inhibited in ras-transformed fibroblasts [19].
  • Expression of lysyl oxidase was almost completely down-regulated in two clones of H-ras-transformed 208F cells (FE-8 and FE-56) [20].
  • Data show that BMP-1 Inhibitor dose dependently inhibits lysyl oxidase activation by up to 50% in undifferentiated proliferating cells [21].

Other interactions of Lox


Analytical, diagnostic and therapeutic context of Lox


  1. Lysyl oxidase is required for vascular and diaphragmatic development in mice. Hornstra, I.K., Birge, S., Starcher, B., Bailey, A.J., Mecham, R.P., Shapiro, S.D. J. Biol. Chem. (2003) [Pubmed]
  2. Lysyl oxidase is essential for normal development and function of the respiratory system and for the integrity of elastic and collagen fibers in various tissues. Mäki, J.M., Sormunen, R., Lippo, S., Kaarteenaho-Wiik, R., Soininen, R., Myllyharju, J. Am. J. Pathol. (2005) [Pubmed]
  3. Copper metabolism in mottled mouse mutants: copper therapy of brindled (Mobr) mice. Mann, J.R., Camakaris, J., Danks, D.M., Walliczek, E.G. Biochem. J. (1979) [Pubmed]
  4. Downregulation of lysyl oxidase in cadmium-resistant fibroblasts. Li, W., Chou, I.N., Boak, A., Kagan, H.M. Am. J. Respir. Cell Mol. Biol. (1995) [Pubmed]
  5. Transient expression of lysyl oxidase by liver myofibroblasts in murine schistosomiasis. Sommer, P., Gleyzal, C., Raccurt, M., Delbourg, M., Serrar, M., Joazeiro, P., Peyrol, S., Kagan, H., Trackman, P.C., Grimaud, J.A. Lab. Invest. (1993) [Pubmed]
  6. Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Marino, S., Vooijs, M., van Der Gulden, H., Jonkers, J., Berns, A. Genes Dev. (2000) [Pubmed]
  7. Inducible transgenic mice reveal resting dendritic cells as potent inducers of CD8+ T cell tolerance. Probst, H.C., Lagnel, J., Kollias, G., van den Broek, M. Immunity (2003) [Pubmed]
  8. Analysis of C-MYC function in normal cells via conditional gene-targeted mutation. de Alboran, I.M., O'Hagan, R.C., Gärtner, F., Malynn, B., Davidson, L., Rickert, R., Rajewsky, K., DePinho, R.A., Alt, F.W. Immunity (2001) [Pubmed]
  9. Deletion of the CD4 silencer element supports a stochastic mechanism of thymocyte lineage commitment. Leung, R.K., Thomson, K., Gallimore, A., Jones, E., Van den Broek, M., Sierro, S., Alsheikhly, A.R., McMichael, A., Rahemtulla, A. Nat. Immunol. (2001) [Pubmed]
  10. Interleukin-10 inhibits tumor metastasis through an NK cell-dependent mechanism. Zheng, L.M., Ojcius, D.M., Garaud, F., Roth, C., Maxwell, E., Li, Z., Rong, H., Chen, J., Wang, X.Y., Catino, J.J., King, I. J. Exp. Med. (1996) [Pubmed]
  11. Chromophore-modified bis-naphthalimides: synthesis and antitumor activity of bis-dibenz[de,h]isoquinoline-1,3-diones. Braña, M.F., Castellano, J.M., Perron, D., Maher, C., Conlon, D., Bousquet, P.F., George, J., Qian, X.D., Robinson, S.P. J. Med. Chem. (1997) [Pubmed]
  12. Lysyl oxidase and collagenase in experimental acute and chronic liver injury. Carter, E.A., McCarron, M.J., Alpert, E., Isselbacher, K.J. Gastroenterology (1982) [Pubmed]
  13. The mouse lysyl oxidase gene (Lox) resides on chromosome 18. Chang, Y.S., Svinarich, D.M., Yang, T.P., Krawetz, S.A. Cytogenet. Cell Genet. (1993) [Pubmed]
  14. Autocrine growth factor regulation of lysyl oxidase expression in transformed fibroblasts. Palamakumbura, A.H., Sommer, P., Trackman, P.C. J. Biol. Chem. (2003) [Pubmed]
  15. Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina. Drewes, P.G., Yanagisawa, H., Starcher, B., Hornstra, I., Csiszar, K., Marinis, S.I., Keller, P., Word, R.A. Am. J. Pathol. (2007) [Pubmed]
  16. Regulation of collagen deposition and lysyl oxidase by tumor necrosis factor-alpha in osteoblasts. Pischon, N., Darbois, L.M., Palamakumbura, A.H., Kessler, E., Trackman, P.C. J. Biol. Chem. (2004) [Pubmed]
  17. Transformation of revertant murine cells by 5-azacytidine results in rapid inhibition of lysyl oxidase expression. Yeh, T.J., Contente, S., Friedman, R.M. Acta microbiologica et immunologica Hungarica. (2005) [Pubmed]
  18. Lysyl oxidase inhibits ras-mediated transformation by preventing activation of NF-kappa B. Jeay, S., Pianetti, S., Kagan, H.M., Sonenshein, G.E. Mol. Cell. Biol. (2003) [Pubmed]
  19. Comparative functional study of the lysyl oxidase promoter in fibroblasts, Ras-transformed fibroblasts, myofibroblasts and smooth muscle cells. Reynaud, C., Gleyzal, C., Jourdan-Le Saux, C., Sommer, P. Cell. Mol. Biol. (Noisy-le-grand) (1999) [Pubmed]
  20. Up-regulation of lysyl oxidase in spontaneous revertants of H-ras-transformed rat fibroblasts. Hajnal, A., Klemenz, R., Schäfer, R. Cancer Res. (1993) [Pubmed]
  21. A procollagen C-proteinase inhibitor diminishes collagen and lysyl oxidase processing but not collagen cross-linking in osteoblastic cultures. Pischon, N., Babakhanlou-Chase, H., Darbois, L., Ho, W.B., Brenner, M.C., Kessler, E., Palamakumbura, A.H., Trackman, P.C. J. Cell. Physiol. (2005) [Pubmed]
  22. The propeptide domain of lysyl oxidase induces phenotypic reversion of ras-transformed cells. Palamakumbura, A.H., Jeay, S., Guo, Y., Pischon, N., Sommer, P., Sonenshein, G.E., Trackman, P.C. J. Biol. Chem. (2004) [Pubmed]
  23. Structural and functional diversity of lysyl oxidase and the LOX-like proteins. Molnar, J., Fong, K.S., He, Q.P., Hayashi, K., Kim, Y., Fong, S.F., Fogelgren, B., Szauter, K.M., Mink, M., Csiszar, K. Biochim. Biophys. Acta (2003) [Pubmed]
  24. Inactivation of the lysyl oxidase gene Lox leads to aortic aneurysms, cardiovascular dysfunction, and perinatal death in mice. Mäki, J.M., Räsänen, J., Tikkanen, H., Sormunen, R., Mäkikallio, K., Kivirikko, K.I., Soininen, R. Circulation (2002) [Pubmed]
  25. Inhibition of aortic aneurysm development in blotchy mice by beta adrenergic blockade independent of altered lysyl oxidase activity. Moursi, M.M., Beebe, H.G., Messina, L.M., Welling, T.H., Stanley, J.C. J. Vasc. Surg. (1995) [Pubmed]
  26. Retinoic acid prevents downregulation of ras recision gene/lysyl oxidase early in adipocyte differentiation. Dimaculangan, D.D., Chawla, A., Boak, A., Kagan, H.M., Lazar, M.A. Differentiation (1994) [Pubmed]
  27. Up-regulation and altered distribution of lysyl oxidase in the central nervous system of mutant SOD1 transgenic mouse model of amyotrophic lateral sclerosis. Li, P.A., He, Q., Cao, T., Yong, G., Szauter, K.M., Fong, K.S., Karlsson, J., Keep, M.F., Csiszar, K. Brain Res. Mol. Brain Res. (2004) [Pubmed]
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