Journal of Biological Chemistry
Volume 278, Issue 12, 21 March 2003, Pages 10257-10263
Journal home page for Journal of Biological Chemistry

ENZYME CATALYSIS AND REGULATION
Identification of Two Novel Nuclear Import Sequences on the 5-Lipoxygenase Protein*

https://doi.org/10.1074/jbc.M211021200Get rights and content
Under a Creative Commons license
open access

The nuclear import of 5-lipoxygenase modulates its capacity to produce leukotrienes from arachidonic acid. However, the molecular determinants of its nuclear import are unknown. Recently, we used structural and functional criteria to identify a novel import sequence at Arg518 on human 5-lipoxygenase (Jones, S. M., Luo, M., Healy, A. M., Peters-Golden, M., and Brock, T. G. (2002) J. Biol. Chem. 277, 38550–38556). However, this analysis also indicated that other import sequences must exist. Here, we identify two additional sites, at Arg112 and Lys158, as nuclear import sequences. Both sites were found to be common to 5-lipoxygenases from different species but not found on other lipoxygenases. Both sites also appeared to be a part of structures that were predominantly random loops. Peptide sequences at these sites were sufficient to direct nuclear import of green fluorescent protein. Mutation of basic residues in these sites impaired nuclear import and combinations of mutations at different sites were additive in effect. Mutations in all three sites were required to disable nuclear accumulation of 5-lipoxygenase in all cells. Significantly, mutation in these sites did not inhibit catalytic function. Taken together, these results indicate that nuclear import of 5-lipoxygenase may reflect the combined functional effects of three discrete import sequences. Mutation of individual sites can, by itself, impair nuclear import, which in turn could impact arachidonic acid metabolism.

Cited by (0)

Published, JBC Papers in Press, January 13, 2003, DOI 10.1074/jbc.M211021200

*

This work was supported by National Institutes of Health Grants R29 AI43574 and R21 AI48141.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.