JNK is associated with Bcl-2 and PP1 in mitochondria: paclitaxel induces its activation and its association with the phosphorylated form of Bcl-2
| Autor: | Annie Valette, Gabrielle Cazettes, Laetitia Brichese |
|---|---|
| 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) |
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Cell cycle checkpoint
Time Factors Mitochondrion 0302 clinical medicine Cytosol MESH: Cytosol Phosphoprotein Phosphatases Phosphorylation 0303 health sciences Kinase Cell biology Mitochondria Protein Transport Proto-Oncogene Proteins c-bcl-2 030220 oncology & carcinogenesis Cell fractionation MESH: Protein Transport MESH: Enzyme Activation MESH: Cell Line Tumor Paclitaxel MESH: Mitochondria Immunocytochemistry Phosphatase Mitosis [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Cyclin B Models Biological 03 medical and health sciences Cell Line Tumor MESH: Phosphoprotein Phosphatases Mitotic Index Humans MESH: Paclitaxel Molecular Biology 030304 developmental biology MESH: Mitotic Index MESH: Humans MESH: Phosphorylation MESH: Time Factors JNK Mitogen-Activated Protein Kinases MESH: Models Biological Cell Biology MESH: Cyclin B MESH: JNK Mitogen-Activated Protein Kinases MESH: Mitosis Enzyme Activation MESH: Hela Cells MESH: Proto-Oncogene Proteins c-bcl-2 Developmental Biology HeLa Cells |
| Zdroj: | Cell Cycle Cell Cycle, Taylor & Francis, 2004, 3 (10), pp.1312-9 |
| ISSN: | 1538-4101 1551-4005 |
| Popis: | It has been shown that the activation of JNK after paclitaxel-induced microtubule damage is parallel to Bcl-2 phosphorylation, cell cycle arrest in mitosis and apoptosis. Using subcellular fractionation and immunocytochemistry, we found here that a pool of activated JNK is located in mitochondria of HeLa cells treated with paclitaxel. Furthermore, whereas the JNK protein is present in a tripartite complex with the anti-apoptotic Bcl-2 protein and the PP1 phosphatase in mitochondria isolated from control cells, the activated form of JNK was associated with the phosphorylated form of Bcl-2, but devoid of PP1, in mitochondria isolated from paclitaxel-treated cells. Moreover, using an original cell-free system, we evidenced a direct involvement of JNK as the kinase responsible for the phosphorylation of mitochondrial Bcl-2 in mitotic arrested cells. Indeed, cytosols prepared from mitotic arrested cells led to a dose-dependent phosphorylation of mitochondrial Bcl-2. Bcl-2 phosphorylation was inhibited by CEP 11004, a JNK pathway inhibitor and by immunodepletion of JNK. Taken together, these data show that JNK activation provides a molecular linkage from microtubule damages to the mitochondrial apoptotic machinery and also point to a pivotal role for the JNK/Bcl-2/PP1 complex in the control of apoptosis following paclitaxel treatment. |
| Databáze: | OpenAIRE |
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