Kawamura Kazue, Murray James A H, Shinmyo Atsuhiko, Sekine Masami
Graduate School of Biological Sciences, Nara Institute of Science and Technology (NAIST), Takayama, Ikoma, Japan.
Plant Mol Biol. 2006 May;61(1-2):311-27. doi: 10.1007/s11103-006-0014-y.
Tobacco (Nicotiana tabacum L.) cv Bright Yellow-2 (BY-2) cells are the most highly synchronizable plant cell culture, and previously we used them to analyze cell cycle regulation of cyclin-dependent kinases (CDKs) containing the cyclin binding motifs PSTAIRE (CDKA) and PPTA/TLRE (CDKB). Here we describe the analysis of tobacco CycD3 cyclins whose transcripts predominantly accumulate during G2 to M phase, which represents a unique feature of this type of cyclin D in plants. Although protein levels of CycD3s fluctuate with different patterns during the cell cycle, kinase assays revealed that the CycD3-associated kinases phosphorylate histone H1 and the tobacco retinoblastoma related protein (NtRBR1) with two peaks at the G1/S and G2/M boundaries. In vitro pull-down assays revealed that cell cycle-regulated CycD3s bind to CDKA, but more weakly than does CycD3;3, and that they also bind to CDKB and the CDK inhibitor NtKIS1a. Mutations in the cyclin box of the CycD3s showed that two amino acids are required for binding with CDKA and NtKIS1a, but no diminished interaction was observed with CDKB. A reconstituted kinase assay was adapted for use with bacterially produced GST-CycD3s, and kinase activity could be activated by incubation of extracts from exponentially growing BY-2 cells. Such activated complexes contained CDKA and CDKB, and the reconstituted GST-CycD3 mutants, retaining binding ability to CDKB, showed kinase activity, suggesting that these cell cycle-regulated CycD3s form active complexes with both A- and B-type CDKs in vitro.
烟草(Nicotiana tabacum L.)品种亮黄-2(BY-2)细胞是最易于同步化的植物细胞培养物,此前我们利用它们来分析含有细胞周期蛋白结合基序PSTAIRE(CDKA)和PPTA/TLRE(CDKB)的细胞周期蛋白依赖性激酶(CDK)的细胞周期调控。在此,我们描述了对烟草CycD3细胞周期蛋白的分析,其转录本主要在G2期到M期积累,这是植物中此类细胞周期蛋白D的一个独特特征。尽管CycD3s的蛋白质水平在细胞周期中呈现不同的波动模式,但激酶分析表明,与CycD3相关的激酶使组蛋白H1和烟草视网膜母细胞瘤相关蛋白(NtRBR1)磷酸化,在G1/S和G2/M边界处出现两个峰值。体外下拉分析表明,受细胞周期调控的CycD3s与CDKA结合,但结合力比CycD3;3弱,并且它们还与CDKB和CDK抑制剂NtKIS1a结合。CycD3s细胞周期蛋白框中的突变表明,与CDKA和NtKIS1a结合需要两个氨基酸,但与CDKB的相互作用未观察到减弱。一种重组激酶分析方法适用于细菌产生的GST-CycD3s,通过培养指数生长的BY-2细胞提取物可激活激酶活性。这种激活的复合物包含CDKA和CDKB,并且保留了与CDKB结合能力的重组GST-CycD3突变体显示出激酶活性,这表明这些受细胞周期调控的CycD3s在体外与A类和B类CDK形成活性复合物。