Open AccessBacterial cyclomodulin Cif blocks the host cell cycle by stabilizing the cyclin‐dependent kinase inhibitors p21 waf1 and p27 kip1
Author(s) -
SambaLouaka Ascel,
Nougayrède JeanPhilippe,
Watrin Claude,
Jubelin Grégory,
Oswald Eric,
Taieb Frédéric
Publication year - 2008
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2008.01224.x
Subject(s) - biology , cell cycle , cyclin dependent kinase 1 , microbiology and biotechnology , cyclin b , mitosis , kinase , cyclin a , cyclin , cell cycle checkpoint , cyclin b1 , cell , biochemistry
Summary 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 G 2 /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 G 2 , but also G 1 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.