周期蛋白 A 通过与复制许可因子 Mcm7 相互作用促进 S 期进入。
Cyclin A promotes S-phase entry via interaction with the replication licensing factor Mcm7.
机构信息
Department of Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
出版信息
Mol Cell Biol. 2011 Jan;31(2):248-55. doi: 10.1128/MCB.00630-10. Epub 2010 Nov 15.
Cyclin A is known to promote S-phase entry in mammals, but its critical targets in this process have not been defined. We derived a novel human cyclin A mutant (CycA-C1), which can activate cyclin-dependent kinase but cannot promote S-phase entry, and isolated replication licensing factor Mcm7 as a factor that interacts with the wild-type cyclin A but not with the mutant. We demonstrated that human cyclin A and Mcm7 interact in the chromatin fraction. To address the physiological significance of the cyclin A-Mcm7 interaction, we isolated an Mcm7 mutant (Mcm7-3) that is capable of association with CycA-C1 and found that it can also suppress the deficiency of CycA-C1 in promoting S-phase entry. Finally, RNA interference experiments showed that the CycA-C1 mutant is defective for the endogenous cyclin A function in S-phase entry and that this defect can be suppressed by the Mcm7-3 mutant. Our findings demonstrate that interaction with Mcm7 is essential for the function of cyclin A in promoting S-phase entry.
周期蛋白 A 已知能促进哺乳动物的 S 期进入，但在这个过程中，其关键靶标尚未确定。我们得到了一种新型的人类周期蛋白 A 突变体（CycA-C1），它可以激活细胞周期蛋白依赖性激酶，但不能促进 S 期进入，并分离出复制许可因子 Mcm7 作为与野生型周期蛋白 A 相互作用但不与突变体相互作用的因子。我们证明人类周期蛋白 A 和 Mcm7 在染色质部分相互作用。为了解周期蛋白 A-Mcm7 相互作用的生理意义，我们分离出一种能够与 CycA-C1 结合的 Mcm7 突变体（Mcm7-3），并发现它也可以抑制 CycA-C1 促进 S 期进入的缺陷。最后，RNA 干扰实验表明，CycA-C1 突变体在 S 期进入中对内源性周期蛋白 A 功能有缺陷，而这种缺陷可以被 Mcm7-3 突变体抑制。我们的研究结果表明，与 Mcm7 的相互作用对于周期蛋白 A 促进 S 期进入的功能是必不可少的。
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