CFTR inhibitory factor

Ribbon diagram of the Cif dimer from P. aeruginosa PA14. From PDB: 3KD2​.

The CFTR inhibitory factor (Cif) is a protein virulence factor secreted by the Gram-negative bacteria Pseudomonas aeruginosa[1] and Acinetobacter nosocomialis.[2] 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),[1] and P-glycoprotein[3] by interfering with the host deubiquitinating machinery.[4] By promoting the ubiquitin-mediated degradation of CFTR, Cif is able to phenocopy cystic fibrosis at the cellular level.[1][5] The cif gene is transcribed as part of a 3 gene operon, whose expression is negatively regulated by CifR, a TetR family repressor.[6]

  1. ^ a b c MacEachran DP, Ye S, Bomberger JM, Hogan DA, Swiatecka-Urban A, Stanton BA, O'Toole GA (2007). "The Pseudomonas aeruginosa Secreted Protein PA2934 Decreases Apical Membrane Expression of the Cystic Fibrosis Transmembrane Conductance Regulator". Infect Immun. 75 (8): 3902–3912. doi:10.1128/IAI.00338-07. PMC 1951978. PMID 17502391.
  2. ^ Bahl CD, Hvorecny KL, Bridges AA, Ballok AE, Bomberger JM, Cady KC, O'Toole GA, Madden DR (2014). "Signature motifs identify an Acinetobacter Cif virulence factor with epoxide hydrolase activity". J Biol Chem. 289 (11): 7460–7469. doi:10.1074/jbc.M113.518092. PMC 3953260. PMID 24474692.
  3. ^ Ye S, MacEachran DP, Hamilton JW, O'Toole GA, Stanton BA (2008). "Chemotoxicity of doxorubicin and surface expression of P-glycoprotein (MDR1) is regulated by the Pseudomonas aeruginosa toxin Cif". Am J Physiol Cell Physiol. 295 (3): C807–18. doi:10.1152/ajpcell.00234.2008. PMC 2544439. PMID 18650266.
  4. ^ Bomberger JM, Ye S, Maceachran DP, Koeppen K, Barnaby RL, O'Toole GA, Stanton BA (2011). Rohde J (ed.). "A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system". PLOS Pathog. 7 (3): e1001325. doi:10.1371/journal.ppat.1001325. PMC 3063759. PMID 21455491.
  5. ^ Swiatecka-Urban A, Moreau-Marquis S, Maceachran DP, Connolly JP, Stanton CR, Su JR, Barnaby R, O'toole GA, Stanton BA (2006). "Pseudomonas aeruginosa inhibits endocytic recycling of CFTR in polarized human airway epithelial cells". Am J Physiol Cell Physiol. 290 (3): C862–72. doi:10.1152/ajpcell.00108.2005. PMID 16236828. S2CID 25992846.
  6. ^ MacEachran DP, Stanton BA, O'Toole GA (2008). "Cif is negatively regulated by the TetR family repressor CifR". J Bacteriol. 76 (7): 3197–3206. doi:10.1128/IAI.00305-08. PMC 2446692. PMID 18458065.