Distinct signaling pathways of microtubule inhibitors--vinblastine and Taxol induce JNK-dependent cell death but through AP-1-dependent and AP-1-independent mechanisms, respectively.

摘要: Vinblastine and paclitaxel (Taxol) are widely used chemotherapeutic drugs that inhibit the normal function of microtubules causing mitotic arrest cell death. Despite these similarities, signaling pathways mediate regulate death induced by agents remain incompletely understood. The purpose this study was to directly compare two in terms their ability activate components c-Jun N-terminal protein kinase (JNK) pathway, establish importance events apoptosis agents. We show both induce subsequent apoptotic with highly similar kinetics JNK c-jun mRNA expression. Surprisingly, vinblastine phosphorylation transcriptional activation, although Taxol failed do so. However, inhibition or an absence protected against vinblastine- Taxol-induced These results suggest activation plays important role agents, differ markedly respect downstream JNK, AP-1-dependent -independent mechanisms, respectively. In addition, show, contrary popular belief, is not necessarily accompanied thus obligate substrate JNK.