MEKK1 is essential for DT40 cell apoptosis in response to microtubule disruption

Vinblastine and other microtubule-damaging agents, such as nocodazole and p aclitaxel, cause cell cycle arrest at the G(2)/M transition and promote apo ptosis in eukaryotic cells. The roles of these drugs in disrupting microtub ule dynamics and causing cell cycle arrest are well characterized. However, the mechanisms by which these agents promote apoptosis are poorly understo od. We disrupted the MEKK1 kinase domain in chicken bursal B-cell line DT40 by homologous recombination and have shown that it is essential for both v inblastine-mediated apoptosis and vinblastine-mediated c-jun N-terminal pro tein kinase activation. In addition, our data indicate that vinblastine-med iated apoptosis in DT40 cells requires new protein synthesis but does not r equire G(2)/M arrest, suggesting that vinblastine-mediated cell cycle arres t and apoptosis are two independent processes.