Characterization of the interaction of human 5-lipoxygenase with its activating protein FLAP

Biochimica Et Biophysica Acta
Ann-Kathrin HäfnerDieter Steinhilber

Abstract

Human 5-lipoxygenase (5-LO) is the key enzyme in the formation of leukotrienes (LTs), important mediators of inflammation. Cellular 5-LO activity is regulated in a complex manner, e.g. by calcium influx, the cellular redox status or 5-LO phosphorylation. Being a mobile enzyme, 5-LO migrates from the cytosol to the nuclear envelope where it is believed to interact with 5-lipoxygenase-activating protein (FLAP) and receives the substrate arachidonic acid (AA). 5-LO contains four cysteine residues located close to the AA entry site. In the present study, we show that in vitro glutathionylation of recombinant purified 5-LO wildtype (WT) as well as 5-LO 4C, a mutant where the four surface cysteines are replaced by serines (Cys159/300/416/418Ser), does not alter the product synthesis. However, in 5-LO/FLAP-transfected HeLa cells, treatment with the thiol-oxidizing agent diamide which promotes glutathionylation at surface Cys residues led to a decreased LT synthesis by 5-LO WT. In contrast to the WT enzyme, LT formation of the 4C mutant was stimulated by addition of diamide. Immunofluorescence studies in human monocytes and HEK293 cells, expressing 5-LO and FLAP, revealed that diamide prevented the translocation of 5-LO WT whereas it e...Continue Reading

References

Mar 15, 1989·Biochemical and Biophysical Research Communications·S Fiore, C N Serhan
Nov 16, 1987·European Journal of Biochemistry·A Hatzelmann, V Ullrich
Mar 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·S E DahlénB Dahlén
Jan 3, 1995·Proceedings of the National Academy of Sciences of the United States of America·M BrungsD Steinhilber
Oct 24, 1998·Prostaglandins & Other Lipid Mediators·M J CoffeyM Peters-Golden
Apr 9, 1999·Biochemistry·T Hammarberg, O Rådmark
Jul 16, 1999·Biochemical and Biophysical Research Communications·X Z DingT E Adrian
Feb 19, 2000·Biochemical and Biophysical Research Communications·A WächtershäuserJ Stein
Jan 18, 2002·The Journal of Biological Chemistry·Shilpa KulkarniWonhwa Cho
Jan 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Rainer SpanbroekAndreas J R Habenicht
Dec 12, 2003·The Journal of Biological Chemistry·Jennifer F CaplanDavid M Waisman
Oct 11, 2005·Journal of Cellular Biochemistry·Thomas G Brock
Aug 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Marija RakonjacOlof Rådmark
Jun 30, 2007·Science·Andrew D FergusonJoseph W Becker
Jan 12, 2008·Trends in Pharmacological Sciences·Jilly F EvansJohn H Hutchinson
Jan 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Rosa E HansenJakob R Winther
Jan 15, 2011·Science·Nathaniel C GilbertMarcia E Newcomer
Jun 23, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Carlo PergolaOliver Werz
Dec 6, 2011·Biochimica Et Biophysica Acta·Michael HörnigDieter Steinhilber
Sep 28, 2012·Molecular Biology of the Cell·Angela M BairRoy J Soberman
Jul 19, 2013·The Journal of Biological Chemistry·Christina L GrekKenneth D Tew
Nov 12, 2013·Antioxidants & Redox Signaling·Khader AwwadIngrid Fleming
Jul 19, 2014·Proceedings of the National Academy of Sciences of the United States of America·Devaraj BasavarajappaOlof Rådmark
Aug 12, 2014·Biochimica Et Biophysica Acta·Mirjam SchröderDieter Steinhilber

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Citations

Sep 7, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jasmin FettelThorsten J Maier
Nov 18, 2016·PloS One·Ann-Kathrin HäfnerDieter Steinhilber
Aug 16, 2018·The Journal of Clinical Investigation·Jesper Z Haeggström
Dec 18, 2020·Frontiers in Endocrinology·Ali A HajeyahValerie B O'Donnell
Aug 4, 2020·Journal of Molecular Biology·Madhuranayaki Thulasingam, Jesper Z Haeggström

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