Raf-1/MEK/MAPK pathway is necessary for the G2/M transition induced by nocodazole

被引:95
作者
Hayne, C
Tzivion, G
Luo, ZJ
机构
[1] Boston Univ, Sch Med, Evans Dept Med, Endocrinol Sect,Diabet & Metab Res Unit, Boston, MA 02118 USA
[2] Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA
[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Unit, Boston, MA 02114 USA
[4] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv, Boston, MA 02114 USA
[5] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA
关键词
D O I
10.1074/jbc.M002766200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The dynamic balance between polymerization and depolymerization of microtubules is critical for cells to enter and exit mitosis, and drugs that disrupt this balance, such as taxol, colchicine, and nocodazole, arrest the cell cycle in mitosis. Although the Raf/MEK/MAPK pathway can be activated by these drugs, its role in mitosis has not been addressed. Here, we characterize activation of Raf/MEK/MAPK by nocodazole when mitosis is induced. We find that at early time points (up to 3 h) in nocodazole induction, Raf/MEK/MAPK is activated, and inhibition of MAPK activation by a MEK inhibitor, PD98059 or U0126, reduces the number of cells entering mitosis by creating a block at G(2). At later time points and in mitosis, activation of MEK/MAPK is severely inhibited, even though Raf-l activity remains high and can be further increased by growth factor. This inhibition is reversed when cells are released from metaphase and enter G(0)/G(1) phase. In addition, we find that binding of Raf-1 to 14-3-3 is progressively induced by nocodazole, reaching a maximum in mitosis, and that this binding is necessary to maintain mitotic Raf-l activity. Our present study indicates that activation of the Raf/MEK/MAPK pathway is necessary for the G(2)/M progression.
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页码:31876 / 31882
页数:7
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