INRA, USC Molecular and Cellular Pathogenesis of Escherichia coli Infections, Toulouse, F-31300, France.
Toxins (Basel). 2011 Apr;3(4):356-68. doi: 10.3390/toxins3040356. Epub 2011 Mar 29.
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.
周期抑制因子（Cifs）是由多种致病菌产生的 III 型分泌效应子。Cifs 是“环调节素”，可以抑制真核宿主细胞周期，还可以劫持其他关键细胞过程，如控制肌动蛋白网络和细胞凋亡的过程。本文综述了 Cif 的最新研究进展，包括它在肠致病性大肠杆菌中的首次特征描述、在不同致病菌中鉴定的多个同源物，以及对其结构的阐明和最近对其作用模式的破译。Cif 通过对调节 Cullin-Ring-泛素连接酶（CRL）复合物的泛素或类泛素蛋白 NEDD8 的脱酰胺作用，破坏宿主的泛素蛋白酶体系统。对宿主细胞的泛素依赖性降解途径的劫持会导致各种细胞功能的调节，如上皮细胞更新、细胞凋亡和免疫反应。因此，Cif 是宿主-细菌相互作用中持续军备竞赛的有力武器。
