Moderate variations in CDC25B protein levels modulate the response to DNA damaging agents
| Autor: | Bernard Ducommun, Béatrix Bugler, Denis Biard, Bernadette Aressy, Annie Valette |
|---|---|
| Přispěvatelé: | Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| Předmět: |
Cdc25
DNA damage Cell [SDV.BC]Life Sciences [q-bio]/Cellular Biology Genomic Instability 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Spheroids Cellular medicine Humans cdc25 Phosphatases CHEK1 Molecular Biology Mitosis 030304 developmental biology Etoposide 0303 health sciences biology Cell Death Kinase Cell Biology Cell cycle G2-M DNA damage checkpoint 3. Good health Cell biology medicine.anatomical_structure Doxorubicin Gamma Rays 030220 oncology & carcinogenesis biology.protein Cancer research Developmental Biology DNA Damage Mutagens |
| Zdroj: | Europe PubMed Central Cell Cycle Cell Cycle, Taylor & Francis, 2008, 7 (14), pp.2234-40 Scopus-Elsevier |
| ISSN: | 1538-4101 1551-4005 |
| Popis: | CDC25B, one of the three members of the CDC25 dual-specificity phosphatase family, plays a critical role in the control of the cell cycle and in the checkpoint response to DNA damage. CDC25B is responsible for the initial dephosphorylation and activation of the cyclin-dependent kinases, thus initiating the train of events leading to entry into mitosis. The critical role played by CDC25B is illustrated by the fact that it is specifically required for checkpoint recovery and that unscheduled accumulation of CDC25B is responsible for illegitimate entry into mitosis. Here, we report that in p53(-/-) colon carcinoma cells, a moderate increase in the CDC25B level is sufficient to impair the DNA damage checkpoint, to increase spontaneous mutagenesis, and to sensitize cells to ionising radiation and genotoxic agents. Using a tumour cell spheroid assay as an alternative to animal studies, we demonstrate that the level of CDC25B expression modulates growth inhibition and apoptotic death. Since CDC25B overexpression has been observed in a significant number of human cancers, including colon carcinoma, and is often associated with high grade tumours and poor prognosis, our work suggests that the expression level of CDC25B might be a potential key parameter of the cellular response to cancer therapy. |
| Databáze: | OpenAIRE |
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