Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Singapore, Republic of Singapore.
Department of Chromosome Biology, Max Perutz Labs, University of Vienna, Vienna Biocenter, Vienna, Austria.
PLoS One. 2023 Mar 23;18(3):e0283590. doi: 10.1371/journal.pone.0283590. eCollection 2023.
Cyclin dependent-kinase 2 (CDK2) plays important functions during the mitotic cell cycle and also facilitates several key events during germ cell development. The majority of CDK2's known meiotic functions occur during prophase of the first meiotic division. Here, CDK2 is involved in the regulation of meiotic transcription, the pairing of homologous chromosomes, and the maturation of meiotic crossover sites. Despite that some of the CDK2 substrates are known, few of them display functions in meiosis. Here, we investigate potential meiotic CDK2 substrates using in silico and in vitro approaches. We find that CDK2 phosphorylates PMS2 at Thr337, PMS1 at Thr331, and MLH1 in vitro. Phosphorylation of PMS2 affects its interaction with MLH1 to some degree. In testis extracts from mice lacking Cdk2, there are changes in expression of PMS2, MSH2, and HEI10, which may be reflective of the loss of CDK2 phosphorylation. Our work has uncovered a few CDK2 substrates with meiotic functions, which will have to be verified in vivo. A better understanding of the CDK2 substrates will help us to gain deeper insight into the functions of this universal kinase.
周期蛋白依赖性激酶 2（CDK2）在有丝分裂细胞周期中发挥重要功能，并且还促进生殖细胞发育中的几个关键事件。CDK2 的大多数已知减数分裂功能发生在第一次减数分裂的前期。在这里，CDK2 参与减数分裂转录的调节、同源染色体的配对以及减数分裂交叉点的成熟。尽管已经知道 CDK2 的一些底物，但其中很少有显示出减数分裂功能。在这里，我们使用计算机模拟和体外方法来研究潜在的减数分裂 CDK2 底物。我们发现 CDK2 在体外磷酸化 PMS2 的 Thr337、PMS1 的 Thr331 和 MLH1。PMS2 的磷酸化在某种程度上影响其与 MLH1 的相互作用。在缺乏 Cdk2 的小鼠睾丸提取物中，PMS2、MSH2 和 HEI10 的表达发生变化，这可能反映了 CDK2 磷酸化的丧失。我们的工作已经发现了一些具有减数分裂功能的 CDK2 底物，这些底物还必须在体内进行验证。对 CDK2 底物的更好理解将帮助我们更深入地了解这种通用激酶的功能。
