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KMID : 0380219990320040379
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Journal of Biochemistry and Molecular Biology
1999 Volume.32 No. 4 p.379 ~ p.384
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Taxol-Induced Apoptosis and Nuclear Translocation of Mitogen-Activated Protein (MAP) Kinase in HeLa Cells
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Kim Sung-Su
Kim Yoon-Suk
Jung Yon-Woo
Choi Hyun-Il
Shim Moon-Jeong
Kim Tae-Ue
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Abstract
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Taxol, a natural product with significant anti-tumor activity, stabilizes microtubules and arrests cells in the G2/M phase of the cell cycle. It has been reported that taxol has additional effects on the cell such as an increase in tyrosine phosphorylation of proteins and activation of mitogen-activated protein (MAP) kinase. This phosphorylated kinase translocates into the nucleus and phosphorylates its substrate c-jun, c-fos, ATF2, and ATF3. The MAP kinase family is comprised of key regulatory proteins that control the cellular response to both proliferation and stress signals. First examination was cytotoxicity and apoptosis-induced concentration with paclitaxel in HeLa cell. A half-maximal inhibition of cell proliferation (IC50) occurred at 13 nM paclitaxel. When DNA fragmentation was analyzed by agarose gel electrophoresis, a nucleosomal ladder became evident 24 h after a taxol (50 nM) addition to the cells. In addition, an apoptotic body was detected by electron microscopy. Taxol-treated cells were arrested at the S phase at 10 nM. Treatment of 50 nM taxol activated the extracellular signal-regulated protein kinase (ERK1), and a fraction of the activated MAP kinases entered the nucleus. It was also discovered that nucleus substrates c-jun was phosphorylated and activated in the cell. The activated ERK1 could subsequently translocate into the nucleus and phosphorylate its substrate c-jun as well. This study suggests that taxol-induced apoptosis might be related with signal transduction via MAP kinases.
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KEYWORD
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Anti-tumor activity, c-jun, DNA fragmentation, MAP kinase, Taxol
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