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Study of the cytolethal distending toxin (CDT)‐activated cell cycle checkpoint
Author(s) -
Alby Frédéric,
Mazars Raoul,
de Rycke Jean,
Guillou Emmanuelle,
Baldin Véronique,
Darbon Jean-Marie,
Ducommun Bernard
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02205-0
Subject(s) - g2 m dna damage checkpoint , chek1 , checkpoint kinase 2 , cell cycle checkpoint , microbiology and biotechnology , cyclin dependent kinase 1 , cytolethal distending toxin , wortmannin , kinase , mitosis , cell cycle , dna damage , spindle checkpoint , biology , cancer research , chemistry , cell , toxin , dna , cell division , spindle apparatus , biochemistry , phosphatidylinositol , microbial toxins
The bacterial cytolethal distending toxin (CDT) triggers a G2/M cell cycle arrest in eukaryotic cells by inhibiting the CDC25C phosphatase‐dependent CDK1 dephosphorylation and activation. We report that upon CDT treatment CDC25C is fully sequestered in the cytoplasmic compartment, an effect that is reminiscent of DNA damage‐dependent checkpoint activation. We show that the checkpoint kinase CHK2, an upstream regulator of CDC25C, is phosphorylated and activated after CDT treatment. In contrast to what is observed with other DNA damaging agents, we demonstrate that the activation of CHK2 can only take place during S‐phase. Use of wortmannin and caffeine suggests that this effect is not dependent on ATM but rather on another as yet unidentified PI3 kinase family member. These results confirm that the CDT is therefore responsible for specific genomic injuries that block cell proliferation by activating a cell cycle checkpoint.