Quantitative Reconstitution of Mitotic CDK1 Activation in Somatic Cell Extracts

被引：92

作者：

Deibler, Richard W. ^{[1
]}

Kirschner, Marc W. ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

来源：

MOLECULAR CELL | 2010年 / 37卷 / 06期

基金：

美国国家卫生研究院;

关键词：

HUMAN CYCLIN-A; KINASE WEE1; XENOPUS; INHIBITOR; MITOSIS; INACTIVATION; OSCILLATOR; MECHANISM; B1-CDK1; CDC25B;

D O I：

10.1016/j.molcel.2010.02.023

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

The regulation of mitotic entry in somatic cells differs from embryonic cells, yet it is only for embryonic cells that we have a quantitative understanding of this process. To gain a similar insight into somatic cells, we developed a human cell extract system that recapitulates CDK1 activation and nuclear envelope breakdown in response to mitotic cyclins. As cyclin B concentrations increase, CDK1 activates in a three-stage nonlinear response, creating an ordering of substrate phosphorylations. This response is established by dual regulatory feedback loops involving WEE1/MYT1, which impose a cyclin B threshold, and CDC25, which allows CDK1 to escape the WEE1/MYT1 inhibition. This system also exhibits a complex response to cyclin A. Cyclin A promotes WEE1 phosphorylation to weaken the negative feedback loop and primes mitotic entry through cyclin B. This observation explains the requirement of both cyclin A and cyclin B to initiate mitosis in somatic cells.

引用

页码：753 / 767

页数：15

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