Role of c-Jun in cellular sensitivity to the microtubule inhibitor vinblastine.
Role of c-Jun in cellular sensitivity to the microtubule inhibitor vinblastine.
复制标题
c-Jun 在细胞对微管抑制剂长春花碱敏感性中的作用。
DOI：
10.1016/j.bbrc.2005.07.194
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Chambers,TimothyC
中科院分区：
文献类型：
--
作者：
Obey,ToriaB;Lyle,ChristopherS;Chambers,TimothyC
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 (1–3nM) 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 IC50of 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.
