Samba-Louaka Ascel, Nougayrède Jean-Philippe, Watrin Claude, Jubelin Grégory, Oswald Eric, Taieb Frédéric
INRA, UMR 1225, F-31076 Toulouse, France.
Cell Microbiol. 2008 Dec;10(12):2496-508. doi: 10.1111/j.1462-5822.2008.01224.x. Epub 2008 Aug 13.
The cycle inhibiting factor (Cif) is a cyclomodulin produced by enteropathogenic and enterohemorrhagic Escherichia coli. Upon injection into the host cell by the bacterial type III secretion system, Cif inhibits the G2/M transition via sustained inhibition of the mitosis inducer CDK1 independently of the DNA damage response. In this study, we show that Cif induces not only G2, but also G1 cell cycle arrest depending on the stage of cells in the cell cycle during the infection. In various cell lines including differentiated and untransformed enterocytes, the cell cycle arrests are correlated with the accumulation of the cyclin-dependent kinase inhibitors p21(waf1/cip1) and p27(kip1). Cif-induced cyclin-dependent kinase inhibitor accumulation is independent of the p53 pathway but occurs through inhibition of their proteasome-mediated degradation. Our results provide a direct link between the mode of action of Cif and the host cell cycle control.
周期抑制因子（Cif）是由肠致病性和肠出血性大肠杆菌产生的一种环调节蛋白。通过细菌III型分泌系统注入宿主细胞后，Cif通过持续抑制有丝分裂诱导剂CDK1来抑制G2/M期转换，且不依赖于DNA损伤反应。在本研究中，我们发现，根据感染期间细胞周期所处阶段，Cif不仅会诱导G2期，还会诱导G1期细胞周期停滞。在包括分化和未转化肠上皮细胞在内的各种细胞系中，细胞周期停滞与细胞周期蛋白依赖性激酶抑制剂p21（waf1/cip1）和p27（kip1）的积累相关。Cif诱导的细胞周期蛋白依赖性激酶抑制剂积累不依赖于p53途径，而是通过抑制其蛋白酶体介导的降解而发生。我们的结果提供了Cif作用模式与宿主细胞周期调控之间的直接联系。
