5-Lipoxygenase compartmentalization in granulocytic cells is modulated by an internal bipartite nuclear localizing sequence and nuclear factor kappa B complex formation.

A region of basic amino acids spanning residues 639-656 in the human 5-lipoxygenase sequence resembles a consensus bipartite nuclear localizing sequence. A synthetic peptide consisting of the Kaposi fibroblast growth factor signal sequence fused to the 5-lipoxygenase639-656 bipartite nuclear localizing sequence has a prominent inhibitory effect on 5-lipoxygenase catalysis in ...
granulocytic HL-60 cells activated by calcium ionophor A23187. Recombinant 5-lipoxygenase was not affected by the peptide. The peptide also inhibited redistribution of 5-lipoxygenase from the cytosol to the nuclear membrane of HL-60 cells stimulated by A23187. 5-Lipoxygenase protein was detected in nuclear factor kappaB (NF-kappaB) p65 subunit immunoprecipitate fractions prepared from HL-60 cell lysates. The amount of 5-lipoxygenase protein coimmunoprecipitated by NF-kappaB antiserum was increased following A23187 stimulation. In cells treated with agents that block 5-lipoxygenase translocation to the nucleus, 5-lipoxygenase protein appearing in the NF-kappaB immunoprecipitate was diminished. Our results implicate an internal bipartite nuclear localizing sequence as a regulatory domain that modulates 5-lipoxygenase redistribution and catalysis in granulocytic cells. Additionally, our results suggest that molecular determinants which govern 5-lipoxygenase and NF-kappaB redistribution to the nucleus may be coordinately controlled in granulocytic cells.
Mesh Terms:
Amino Acid Sequence, Arachidonate 5-Lipoxygenase, Cell Compartmentation, Enzyme Activation, Flavonoids, Granulocytes, HL-60 Cells, Humans, Molecular Sequence Data, NF-kappa B, Nuclear Localization Signals, Peptide Fragments, Precipitin Tests, Subcellular Fractions
Arch. Biochem. Biophys.
Date: Aug. 01, 1998
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