Roles of coactosin-like protein (CLP) and 5-lipoxygenase-activating protein (FLAP) in cellular leukotriene biosynthesis
- 5-Lipoxygenase (5LO) is a key enzyme in biosynthesis of leukotrienes (LTs), lipid mediators of inflammation. To study the roles of the 5LO accessory proteins coactosin-like protein (CLP) and 5LO-activating protein (FLAP), we knocked down these proteins in human monocytic cells. Our results show that expression of CLP was required for full cellular 5LO activity when cells were activated with Ca2+ ionophore, as well as with a physiological stimulus (lipopolysaccharide followed by N-formylmethionyl-leucyl-phenylalanine). During LT biosynthesis in stimulated cells, 5LO typically translocates to the nuclear membrane. This redistribution, from cytosolic to perinuclear, was clearly compromised in both CLP- and FLAP-deficient cells. Our results suggest that the CLP–5LO interaction may be a target for reduced LT production.
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| Author: | Devaraj Basavarajappa, Min Wan, Ana Lukic, Dieter SteinhilberORCiDGND, Bengt Samuelsson, Olof RådmarkORCiD |
|---|---|
| URN: | urn:nbn:de:hebis:30:3-352636 |
| DOI: | https://doi.org/10.1073/pnas.1410983111 |
| ISSN: | 0027-8424 |
| ISSN: | 1091-6490 |
| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/25034252 |
| Parent Title (English): | Proceedings of the National Academy of Sciences of the United States of America |
| Publisher: | National Acad. of Sciences |
| Place of publication: | Washington, DC |
| Document Type: | Article |
| Language: | English |
| Year of Completion: | 2014 |
| Date of first Publication: | 2014/07/17 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2014/10/15 |
| Tag: | eicosanoid; inflammation; oxylipin |
| Volume: | 111 |
| Issue: | 31 |
| Page Number: | 6 |
| First Page: | 11371 |
| Last Page: | 11376 |
| Note: | Freely available online through the PNAS open access option. |
| HeBIS-PPN: | 366284576 |
| Institutes: | Biochemie, Chemie und Pharmazie / Biochemie und Chemie |
| Biochemie, Chemie und Pharmazie / Pharmazie | |
| Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
| Sammlungen: | Universitätspublikationen |
| Sammlung Biologie / Sondersammelgebiets-Volltexte | |
| Licence (German): |  Creative Commons - Namensnennung 3.0 |
