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CFTR inhibitory factor : ウィキペディア英語版
CFTR inhibitory factor

The CFTR inhibitory factor (Cif) is a protein virulence factor secreted by the Gram-negative bacteria ''Pseudomonas aeruginosa'' and ''Acinetobacter nosocomialis''. Discovered at Dartmouth Medical School, Cif is able to alter the trafficking of select ABC transporters in eukaryotic epithelial cells, such as the cystic fibrosis transmembrane conductance regulator (CFTR),〔 and P-glycoprotein by interfering with the host deubiquitinating machinery. By promoting the ubiquitin-mediated degradation of CFTR, Cif is able to phenocopy cystic fibrosis at the cellular level. The ''cif'' gene is transcribed as part of a 3 gene operon, whose expression is negatively regulated by CifR, a TetR family repressor.
== Cellular mechanism of action ==
Cif was first discovered by co-culturing ''P. aeruginosa'' with human airway epithelial cells and monitoring the resulting effect on chloride ion efflux across a polarized monolayer. After co-culture, the CFTR specific chloride ion efflux was found to be drastically reduced.〔 This was determined to be caused by reduced levels of CFTR at the apical surface of these cells. This effect was later found to be the result of a single secreted protein produced by ''P. aeruginosa'', which was named the CFTR inhibitory factor for this initial phenotype. Cif is secreted by ''P. aeruginosa'' PA14 as soluble protein as well as packaged into outer membrane vesicles (OMV). Cif is far more potent when applied in OMVs, likely due to efficiency of delivery. Purified, recombinant Cif protein can be applied to polarized monolayers of mammalian cells and promote the removal of CFTR〔 and P-glycoprotein〔 from the apical membrane. Cif accomplishes this by interfering with the host deubiquitylation system.〔

抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)
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