Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique, Université Montpellier 2, Université Montpellier 1, Montpellier, France.
PLoS One. 2011;6(7):e22879. doi: 10.1371/journal.pone.0022879. Epub 2011 Jul 28.
Cyclin A2 is essential at two critical points in the somatic cell cycle: during S phase, when it activates CDK2, and during the G2 to M transition when it activates CDK1. Based on the crystal structure of Cyclin A2 in association with CDKs, we generated a panel of mutants to characterize the specific amino acids required for partner binding, CDK activation and subcellular localization. We find that CDK1, CDK2, p21, p27 and p107 have overlapping but distinct requirements for association with this protein. Our data highlight the crucial importance of the N-terminal α helix, in conjunction with the α3 helix within the cyclin box, in activating CDK. Several Cyclin A2 mutants selectively bind to either CDK1 or CDK2. We demonstrate that association of Cyclin A2 to proteins such as CDK2 that was previously suggested as crucial is not a prerequisite for its nuclear localization, and we propose that the whole protein structure is involved.
细胞周期蛋白 A2 在体细胞周期的两个关键节点中是必不可少的：在 S 期，它激活 CDK2；在 G2 到 M 期过渡时，它激活 CDK1。基于细胞周期蛋白 A2 与 CDKs 的晶体结构，我们生成了一组突变体，以表征伴侣结合、CDK 激活和亚细胞定位所需的特定氨基酸。我们发现 CDK1、CDK2、p21、p27 和 p107 与该蛋白的结合具有重叠但不同的要求。我们的数据突出表明，N 端 α 螺旋与 cyclin 盒内的 α3 螺旋一起，对于激活 CDK 至关重要。几种细胞周期蛋白 A2 突变体选择性地与 CDK1 或 CDK2 结合。我们证明，与之前被认为至关重要的 CDK2 等蛋白的结合并不是其核定位的先决条件，我们提出整个蛋白质结构都参与其中。
