Up-regulation of cdc2 protein during paclitaxel-induced apoptosis

Autor: Annie Valette, Philippe Chadebech, Laetitia Brichese, Isabelle Truchet
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), CHADEBECH, Philippe
Rok vydání: 2000
Předmět:
G2 Phase
Cancer Research
Paclitaxel
Antimetabolites
Cyclin D
Cyclin A
Cyclin B
Apoptosis
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
[SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
[SDV.CAN] Life Sciences [q-bio]/Cancer
Cyclin-dependent kinase
CDC2 Protein Kinase
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Tumor Cells
Cultured
Humans
RNA
Messenger
Cycloheximide
Phosphorylation
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
2-Aminopurine
[SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
Protein Synthesis Inhibitors
Cyclin-dependent kinase 1
biology
urogenital system
Cyclin-dependent kinase 2
DNA
Antineoplastic Agents
Phytogenic
Up-Regulation
3. Good health
Cell biology
Enzyme Activation
Oncology
Biochemistry
[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie
embryonic structures
biology.protein
Cyclin-dependent kinase complex
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
biological phenomena
cell phenomena
and immunity
Cyclin A2
Zdroj: International Journal of Cancer
International Journal of Cancer, Wiley, 2000, 87 (6), pp.779-786. ⟨10.1002/1097-0215(20000915)87:63.0.CO;2-4⟩
International Journal of Cancer, 2000, 87 (6), pp.779-786. ⟨10.1002/1097-0215(20000915)87:63.0.CO;2-4⟩
ISSN: 1097-0215
0020-7136
DOI: 10.1002/1097-0215(20000915)87:6<779::aid-ijc3>3.0.co;2-4
Popis: International audience; Microtubule damages induced by paclitaxel inhibit proteasome-dependent degradation of cyclin B, resulting in a sustained activation of cyclin B/cdc2 kinase and a cell cycle arrest in mitosis. It has been previously shown that this kinase activity is also required for paclitaxel-induced apoptosis. We found here that paclitaxel increased cdc2 mRNA and protein levels and led to an accumulation of cdc2 in the active dephosphorylated form in NIH-OVCAR-3 cells. The addition of cycloheximide inhibited the paclitaxel-induced increase in cdc2 protein level, further indicating that paclitaxel stimulates cdc2 synthesis. This increase in cdc2 synthesis is a consequence of paclitaxel-induced arrest in mitosis. Indeed, dual analysis of DNA and cdc2 protein contents indicated that cdc2 up-regulation occurred in cells arrested with a G2/M DNA content. Furthermore, no up-regulation of cdc2 protein was observed when paclitaxel-treated cells were prevented from entering mitosis by treatment with purvalanol A, a cyclin-dependent kinase (CDK) inhibitor, or stimulated to exit mitosis with 2-AP, a non-specific kinase inhibitor. In addition, when paclitaxel-induced apoptosis was inhibited by Bcl-2 over-expression, cdc2 up-regulation did not occur, leading to a lower level of activation of the cyclin B/cdc2 complex. Taken together, these results indicated that paclitaxel-induced cdc2 protein synthesis participates in a positive feedback loop designed to increase the activity of cyclin B/cdc2 kinase and thus may play a role in paclitaxel-induced apoptosis.
Databáze: OpenAIRE
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