ArticleMolecular and cellular biology2011
Calmodulin antagonizes a calcium-activated SCF ubiquitin E3 ligase subunit, FBXL2, to regulate surfactant homeostasis.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 51 citations in OpenAlex.
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- Palmitoylation and PDE6δ regulate membrane-compartment-specific substrate ubiquitylation and degradation.Cell reports · 2023Article
- Epigenetics alternation in lung fibrosis and lung cancer.Frontiers in cell and developmental biology · 2022Review
- The FBXL family of F-box proteins: variations on a theme.Open biology · 2020Article
- Chemical inhibition of FBXO7 reduces inflammation and confers neuroprotection by stabilizing the mitochondrial kinase PINK1.JCI insight · 2020Article
- GGTase3 is a newly identified geranylgeranyltransferase targeting a ubiquitin ligase.Nature structural & molecular biology · 2019Article
- Tumor suppressive CaCell stress · 2017Article
- miRNA-346 promotes proliferation, migration and invasion in liver cancer.Oncology letters · 2017Article
- Low-intensity pulsed ultrasound (LIPUS) prevents periprosthetic inflammatory loosening through FBXL2-TRAF6 ubiquitination pathway.Scientific reports · 2017Article
- UBE3B Is a Calmodulin-regulated, Mitochondrion-associated E3 Ubiquitin Ligase.The Journal of biological chemistry · 2017Article
- CFL-1, a novel F-box protein with leucine-rich repeat may interact with UNC-10 for the regulation of defecation and daumone response inAnimal cells and systems · 2017Article
- Small molecule therapeutics targeting F-box proteins in cancer.Seminars in cancer biology · 2016Review
- LPS impairs oxygen utilization in epithelia by triggering degradation of the mitochondrial enzyme Alcat1.Journal of cell science · 2016Article
- Cleavage of Signal Regulatory Protein α (SIRPα) Enhances Inflammatory Signaling.The Journal of biological chemistry · 2015Article
- Identification of C-terminal Hsp70-interacting protein as a mediator of tumour necrosis factor action in osteoblast differentiation by targeting osterix for degradation.Journal of cellular and molecular medicine · 2015Article
- The proinflammatory role of HECTD2 in innate immunity and experimental lung injury.Science translational medicine · 2015Article
- The ubiquitin E3 ligase SCF-FBXO24 recognizes deacetylated nucleoside diphosphate kinase A to enhance its degradation.Molecular and cellular biology · 2015Article
- F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7.Cell death & disease · 2015Article
- SCF ubiquitin ligase-targeted therapies.Nature reviews. Drug discovery · 2014Review
- A CULLINary ride across the secretory pathway: more than just secretion.Trends in cell biology · 2014Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Calmodulin is a universal calcium-sensing protein that has pleiotropic effects. Here we show that calmodulin inhibits a new SCF (Skp1-Cullin-F-box) E3 ligase component, FBXL2. During Pseudomonas aeruginosa infection, SCF (FBXL2) targets the key enzyme, CCTα, for its monoubiquitination and degradation, thereby reducing synthesis of the indispensable membrane and surfactant component, phosphatidylcholine. P. aeruginosa triggers calcium influx and calcium-dependent activation of FBXL2 within the Golgi complex, where it engages CCTα. FBXL2 through its C terminus binds to the CCTα IQ motif. FBXL2 knockdown increases CCTα levels and phospholipid synthesis. The molecular interaction of FBXL2 with CCTα is opposed by calmodulin, which traffics to the Golgi complex, binds FBXL2 (residues 80 to 90) via its C terminus, and vies with the ligase for occupancy within the IQ motif. These observations were recapitulated in murine models of P. aeruginosa-induced surfactant deficiency, where calmodulin gene transfer reduced FBXL2 actions by stabilizing CCTα and lessening the severity of inflammatory lung injury. The results provide a unique model of calcium-regulated intermolecular competition between an E3 ligase subunit and an antagonist that is critically relevant to pneumonia and lipid homeostasis.
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Registered trials
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