title: Cycle inhibiting factors (cifs): cyclomodulins that usurp the ubiquitin-dependent degradation pathway of host cells.
abstract: Cycle inhibiting factors (Cifs) are type III secreted effectors produced by diverse pathogenic bacteria. Cifs are "cyclomodulins" that inhibit the eukaryotic host cell cycle and also hijack other key cellular processes such as those controlling the actin network and apoptosis. This review summarizes current knowledge on Cif since its first characterization in enteropathogenic Escherichia coli, the identification of several xenologues in distant pathogenic bacteria, to its structure elucidation and the recent deciphering of its mode of action. Cif impairs the host ubiquitin proteasome system through deamidation of ubiquitin or the ubiquitin-like protein NEDD8 that regulates Cullin-Ring-ubiquitin Ligase (CRL) complexes. The hijacking of the ubiquitin-dependent degradation pathway of host cells results in the modulation of various cellular functions such as epithelium renewal, apoptosis and immune response. Cif is therefore a powerful weapon in the continuous arm race that characterizes host-bacteria interactions.
authors: INRA, USC Molecular and Cellular Pathogenesis of Escherichia coli Infections, Toulouse, F-31300, France. f.taieb@envt.fr
authors: Frédéric
authors: F
authors: Taieb
authors: Jean-Philippe
authors: JP
authors: Nougayrède
authors: Eric
authors: E
authors: Oswald
mesh_terms: D017209:Apoptosis; D058947:Bacterial Secretion Systems; D002453:Cell Cycle; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics / Q000378:metabolism*; D054308:Enteropathogenic Escherichia coli / Q000472:pathogenicity*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D000075687:NEDD8 Protein; D015398:Signal Transduction; D014452:Ubiquitins / Q000235:genetics* / Q000378:metabolism
chemical_list: D058947:Bacterial Secretion Systems; C481998:Cif protein, E coli; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D029968:Escherichia coli Proteins; D000075687:NEDD8 Protein; C082860:NEDD8 protein, human; D014452:Ubiquitins