Nuclear localization of cyclin B1 controls mitotic entry after DNA damage.
Nuclear localization of cyclin B1 controls mitotic entry after DNA damage.
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DOI：
10.1083/jcb.141.4.875
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发表时间：
1998-05-18
影响因子：
7.8
通讯作者：
Morgan, DO
中科院分区：
文献类型：
--
作者：
Jin, P;Hardy, S;Morgan, DO
人类细胞中的有丝分裂由蛋白激酶Cdc 2-细胞周期蛋白B1启动，其在G2末端通过两个抑制性残基Thr 14和Tyr 15的去磷酸化而被激活。DNA损伤后发生的G2期阻滞部分是由于这些位点磷酸化的稳定。我们探讨了进入有丝分裂也受到Cdc 2-细胞周期蛋白B1的亚细胞位置调节的可能性，Cdc 2-细胞周期蛋白B1在G2结束时突然进入细胞核。我们测量了HeLa细胞有丝分裂的时间表达组成型核细胞周期蛋白B1突变体。平行的研究进行了细胞表达Cdc 2AF，Cdc 2突变体，不能在抑制位点磷酸化。而核细胞周期蛋白B1和Cdc 2AF在正常生长条件下几乎没有影响，他们一起诱导一个惊人的过早有丝分裂表型。细胞周期蛋白B1的核靶向在G2期被DNA损伤阻滞的细胞中特别有效，在那里它大大减少了损伤诱导的G2期阻滞。核细胞周期蛋白B1和Cdc 2AF的表达也导致了有丝分裂出口的显着缺陷。因此，细胞周期蛋白B1的核靶向和Cdc 2的去磷酸化都有助于控制人类细胞中有丝分裂的进入和退出。
Mitosis in human cells is initiated by the protein kinase Cdc2-cyclin B1, which is activated at the end of G2 by dephosphorylation of two inhibitory residues, Thr14 and Tyr15. The G2 arrest that occurs after DNA damage is due in part to stabilization of phosphorylation at these sites. We explored the possibility that entry into mitosis is also regulated by the subcellular location of Cdc2-cyclin B1, which is suddenly imported into the nucleus at the end of G2. We measured the timing of mitosis in HeLa cells expressing a constitutively nuclear cyclin B1 mutant. Parallel studies were performed with cells expressing Cdc2AF, a Cdc2 mutant that cannot be phosphorylated at inhibitory sites. Whereas nuclear cyclin B1 and Cdc2AF each had little effect under normal growth conditions, together they induced a striking premature mitotic phenotype. Nuclear targeting of cyclin B1 was particularly effective in cells arrested in G2 by DNA damage, where it greatly reduced the damage-induced G2 arrest. Expression of nuclear cyclin B1 and Cdc2AF also resulted in significant defects in the exit from mitosis. Thus, nuclear targeting of cyclin B1 and dephosphorylation of Cdc2 both contribute to the control of mitotic entry and exit in human cells.
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DOI：
10.1073/pnas.94.2.502
发表时间：
1997-01-21
影响因子：
11.1
作者：
Li, J;Meyer, AN;Donoghue, DJ
通讯作者：
Donoghue, DJ
DOI：
10.1083/jcb.134.4.963
发表时间：
1996-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Jin P;Gu Y;Morgan DO
通讯作者：
Morgan DO
影响因子：
3.3
作者：
Blasina, A;Paegle, ES;McGowan, CH
通讯作者：
McGowan, CH
影响因子：
10.5
作者：
HARDY, S;ENGEL, DA;SHENK, T
通讯作者：
SHENK, T
影响因子：
4
作者：
Lydall, D;Weinert, T
通讯作者：
Weinert, T