ArticleProceedings of the National Academy of Sciences of the United States of America2014
Roles of coactosin-like protein (CLP) and 5-lipoxygenase-activating protein (FLAP) in cellular leukotriene biosynthesis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- A systematic review of serum autoantibodies as biomarkers for pancreatic cancer detection.Oncotarget · 2016Pooled it
- Coactosin-Like Protein Reduces Prostaglandin DAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Hypertensive Pressure Mechanosensing Alone Triggers Lipid Droplet Accumulation and Transdifferentiation of Vascular Smooth Muscle Cells to Foam Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The Cxcr2Frontiers in immunology · 2023Article
- Free docosahexaenoic acid promotes ferroptotic cell death via lipoxygenase dependent and independent pathways in cancer cells.European journal of nutrition · 2022Article
- Theoretical Characterization of the Step-by-Step Mechanism of Conversion of Leukotriene AInternational journal of molecular sciences · 2022Article
- The relevance of CYSLTR1 gene polymorphism to the severity of allergic rhinitis and clinical responsiveness of montelukast in children.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2021Article
- Untangling the web of 5-lipoxygenase-derived products from a molecular and structural perspective: The battle between pro- and anti-inflammatory lipid mediators.Biochemical pharmacology · 2021Review
- Modulation of microRNA processing by 5-lipoxygenase.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Dicer up-regulation by inhibition of specific proteolysis in differentiating monocytic cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The Biosynthesis of Enzymatically Oxidized Lipids.Frontiers in endocrinology · 2020Review
- Coactosin-Like Protein (COTL1) Promotes Glioblastoma (GBM) Growth in vitro and in vivo.Cancer management and research · 2020Article
- Iron-Dependent Trafficking of 5-Lipoxygenase and Impact on Human Macrophage Activation.Frontiers in immunology · 2019Article
- Stabilization and improved activity of arachidonate 11Journal of lipid research · 2018Article
- Leukotriene biosynthetic enzymes as therapeutic targets.The Journal of clinical investigation · 2018Review
- The arachidonic acid metabolism protein-protein interaction network and its expression pattern in esophageal diseases.American journal of translational research · 2018Article
- Androgen-mediated sex bias impairs efficiency of leukotriene biosynthesis inhibitors in males.The Journal of clinical investigation · 2017Article
- Cofilin-1 and Other ADF/Cofilin Superfamily Members in Human Malignant Cells.International journal of molecular sciences · 2016Review
- Pulmonary epithelial cancer cells and their exosomes metabolize myeloid cell-derived leukotriene C4 to leukotriene D4.Journal of lipid research · 2016Article
- 5-Lipoxygenase-activating protein rescues activity of 5-lipoxygenase mutations that delay nuclear membrane association and disrupt product formation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-Lipoxygenase (5LO) is a key enzyme in leukotriene (LT) biosynthesis. Two accessory proteins, coactosin-like protein (CLP) and 5-lipoxygenase-activating protein (FLAP), can support 5LO activity. To study the roles of CLP and FLAP, we knocked down these proteins in the human monocytic cell line Mono Mac 6 (MM6). Expression of CLP increased MM6 cellular 5LO activity for all stimuli tested. CLP is not absolutely crucial, however; some 5LO activity remained in all incubations of CLP knockdown cells. FLAP knockdown had minor effects in the presence of exogenous arachidonic acid, but led to prominent reductions in 5LO product formation from endogenous substrate. Similar effects were observed after CLP and FLAP knockdown in human primary macrophages as well. In addition, FLAP knockdown reduced conversion of leukotriene A4 to leukotriene C4 (LTC4), suggesting a role for the activity of LTC4 synthase. After stimulation of MM6 cells by phorbol myristate acetate and ionophore A23187, a perinuclear ring pattern was observed for 5LO. This redistribution from cytosolic to perinuclear was clearly compromised in both CLP- and FLAP-deficient cells. In addition, association of CLP with the nucleus was almost absent after 5LO knockdown, and was clearly reduced in FLAP knockdown cells. Coimmunoprecipitation experiments indicated that 5LO-CLP complex formation in MM6 cells was increased by stimulation with ionophore, and that this complex was formed to the same extent in FLAP knockdown cells. A possible interpretation of our findings is that on cell stimulation, formation of the 5LO-CLP complex augments the translocation from cytosol to nucleus, whereas FLAP stabilizes association of this complex with the perinuclear membrane.
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