Role of c-Jun in cellular sensitivity to the microtubule inhibitor vinblastine.

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Obey TB, Lyle CS, Chambers TC

Role of c-Jun in cellular sensitivity to the microtubule inhibitor vinblastine.

Biochem Biophys Res Commun. 2005 Oct 7;335(4):1179-84.

PubMed ID

16111654 [ View in PubMed

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Abstract

The role of c-Jun in the apoptotic response of cells to the microtubule inhibitor vinblastine was investigated using fibroblasts lacking or overexpressing c-Jun. c-Jun null cells were found to be more sensitive than wild-type cells at low (1-3 nM) concentrations of vinblastine, but showed essentially identical apoptotic responses as wild-type cells at a higher concentration of 10nM. In contrast, c-Jun overexpressing cells were highly vinblastine-resistant, with an IC50 of 12-fold greater than wild-type cells. The fate of cells exposed to lethal concentrations of vinblastine was examined by propidium iodide staining and flow cytometry. All cell types appeared to undergo mitotic arrest prior to apoptosis. Apoptosis of wild-type cells was associated with significant DNA re-replication. In contrast, DNA re-replication was much less prominent in vinblastine-treated c-Jun null cells and absent during apoptosis of c-Jun overexpressing cells. These results suggest that c-Jun plays a key role in the cellular sensitivity to vinblastine. In addition, c-Jun appears to regulate the pathway to cell death following mitotic arrest.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Vinblastine	Transcription factor AP-1	Protein	Humans	No	Other/unknown	Details