JNK is associated with Bcl-2 and PP1 in mitochondria: paclitaxel induces its activation and its association with the phosphorylated form of Bcl-2. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Cell Cycle Année : 2004

JNK is associated with Bcl-2 and PP1 in mitochondria: paclitaxel induces its activation and its association with the phosphorylated form of Bcl-2.

Résumé

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.

Dates et versions

hal-00317538 , version 1 (03-09-2008)

Identifiants

Citer

Laetitia Brichese, Gabrielle Cazettes, Annie Valette. JNK is associated with Bcl-2 and PP1 in mitochondria: paclitaxel induces its activation and its association with the phosphorylated form of Bcl-2.. Cell Cycle, 2004, 3 (10), pp.1312-9. ⟨10.4161/cc.3.10.1166⟩. ⟨hal-00317538⟩
28 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More