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Gene Review

Alox8  -  arachidonate 8-lipoxygenase

Mus musculus

Synonyms: 15-LOX-2, 15-LOX-B, 15-lipoxygenase 2, 8-LOX, 8S-LOX, ...
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Disease relevance of Alox8


High impact information on Alox8

  • Our results with mutation of the conserved Ala to Gly in two S lipoxygenases (mouse 8S-LOX and human 15-LOX-2) and the corresponding Gly-Ala substitution in two R lipoxygenases (human 12R-LOX and coral 8R-LOX) reveal that the basis for R or S stereo-control also involves a switch in the position of oxygenation on the substrate [4].
  • Murine 8-lipoxygenase (8-LOX), homologue of the 15-LOX-2 enzyme that is expressed in benign human prostatic epithelium and reduced in Pca, was not detected in wild-type or LPB-Tag prostates as determined by enzyme assay, reverse transcription-PCR, and immunohistochemistry [5].
  • We also found that the binding of these proteins to the TRE was significantly increased by TPA treatment and inhibition of the binding by mithramycin A decreased TPA-induced promoter activity as well as 8S-LOX mRNA expression [6].
  • The cloned 8S-LOX promoter ( approximately 2 kb) in which a transcription initiation site was mapped at -27 from the ATG has neither a TATA box nor a CCAAT box [6].
  • Mutation of the corresponding residues in 15-LOX-2 to the 8-LOX sequence changed specificity to 50% oxygenation at C-8 for one amino acid substitution and 70% at C-8 for the double mutant [7].

Biological context of Alox8


Anatomical context of Alox8

  • In this study, we found TPA-induced 8S-LOX mRNA expression is a result of increased transcription in SSIN primary keratinocytes and further investigated transcriptional regulation of 8S-LOX expression by cloning its promoter [6].

Associations of Alox8 with chemical compounds


Regulatory relationships of Alox8


Analytical, diagnostic and therapeutic context of Alox8


  1. An antitumorigenic role for murine 8S-lipoxygenase in skin carcinogenesis. Kim, E., Rundhaug, J.E., Benavides, F., Yang, P., Newman, R.A., Fischer, S.M. Oncogene (2005) [Pubmed]
  2. Upregulation of 8-lipoxygenase in the dermatitis of IkappaB-alpha-deficient mice. Schneider, C., Strayhorn, W.D., Brantley, D.M., Nanney, L.B., Yull, F.E., Brash, A.R. J. Invest. Dermatol. (2004) [Pubmed]
  3. Leukotriene A synthase activity of purified mouse skin arachidonate 8-lipoxygenase expressed in Escherichia coli. Qiao, N., Takahashi, Y., Takamatsu, H., Yoshimoto, T. Biochim. Biophys. Acta (1999) [Pubmed]
  4. A single active site residue directs oxygenation stereospecificity in lipoxygenases: stereocontrol is linked to the position of oxygenation. Coffa, G., Brash, A.R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  5. Elevated expression of 12/15-lipoxygenase and cyclooxygenase-2 in a transgenic mouse model of prostate carcinoma. Shappell, S.B., Olson, S.J., Hannah, S.E., Manning, S., Roberts, R.L., Masumori, N., Jisaka, M., Boeglin, W.E., Vader, V., Dave, D.S., Shook, M.F., Thomas, T.Z., Funk, C.D., Brash, A.R., Matusik, R.J. Cancer Res. (2003) [Pubmed]
  6. Identification and characterization of a phorbol ester-responsive element in the murine 8S-lipoxygenase gene. Kim, E., Muga, S.J., Fischer, S.M. J. Biol. Chem. (2004) [Pubmed]
  7. Identification of amino acid determinants of the positional specificity of mouse 8S-lipoxygenase and human 15S-lipoxygenase-2. Jisaka, M., Kim, R.B., Boeglin, W.E., Brash, A.R. J. Biol. Chem. (2000) [Pubmed]
  8. Arachidonate 8(S)-lipoxygenase. Fürstenberger, G., Marks, F., Krieg, P. Prostaglandins Other Lipid Mediat. (2002) [Pubmed]
  9. Site-directed mutagenesis studies on a putative fifth iron ligand of mouse 8S-lipoxygenase: retention of catalytic activity on mutation of serine-558 to asparagine, histidine, or alanine. Jisaka, M., Boeglin, W.E., Kim, R.B., Brash, A.R. Arch. Biochem. Biophys. (2001) [Pubmed]
  10. 8S-lipoxygenase products activate peroxisome proliferator-activated receptor alpha and induce differentiation in murine keratinocytes. Muga, S.J., Thuillier, P., Pavone, A., Rundhaug, J.E., Boeglin, W.E., Jisaka, M., Brash, A.R., Fischer, S.M. Cell Growth Differ. (2000) [Pubmed]
  11. Molecular cloning and functional expression of a phorbol ester-inducible 8S-lipoxygenase from mouse skin. Jisaka, M., Kim, R.B., Boeglin, W.E., Nanney, L.B., Brash, A.R. J. Biol. Chem. (1997) [Pubmed]
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