Study of the cytolethal distending toxin (CDT)-activated cell cycle checkpoint. Involvement of the CHK2 kinase

Autor: Véronique Baldin, Frédéric Alby, Raoul Mazars, Bernard Ducommun, Jean-Marie Darbon, Emmanuelle Guillou, Jean De Rycke
Přispěvatelé: Microbiologie, Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), ProdInra, Migration
Rok vydání: 2001
Předmět:
Intracellular Fluid
Cell cycle checkpoint
Cytolethal distending toxin
Cell Cycle Proteins
Ataxia Telangiectasia Mutated Proteins
Biochemistry
S Phase
Wortmannin
chemistry.chemical_compound
Structural Biology
Phosphorylation
0303 health sciences
030302 biochemistry & molecular biology
Cell Cycle
Cell cycle
Protein-Tyrosine Kinases
3. Good health
Cell biology
DNA-Binding Proteins
biological phenomena
cell phenomena
and immunity
G2 Phase
Bacterial Toxins
Proto-Oncogene Proteins pp60(c-src)
Biophysics
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Biology
Protein Serine-Threonine Kinases
Cell Line
03 medical and health sciences
Caffeine
Genetics
Humans
cdc25 Phosphatases
CHEK1
Molecular Biology
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
030304 developmental biology
Checkpoint 2 kinase
Cyclin-dependent kinase 1
Cell growth
Tumor Suppressor Proteins
Cell Biology
G2-M DNA damage checkpoint
CDC25C
Androstadienes
Genes
cdc
chemistry
Cancer research
HeLa Cells
Zdroj: FEBS Letters
FEBS Letters, Wiley, 2001, 491, pp.261-265
ISSN: 0014-5793
1873-3468
Popis: 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.
Databáze: OpenAIRE
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