The PITSLRE/CDK11p58 protein kinase promotes centrosome maturation and bipolar spindle formation
The PITSLRE/CDK11p58 protein kinase promotes centrosome maturation and bipolar spindle formation
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DOI：
10.1038/sj.embor.7400639
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发表时间：
2006-04-01
期刊：
影响因子：
7.7
通讯作者：
Giet, R
中科院分区：
文献类型：
--
作者：
Petretti, C;Savoian, M;Giet, R
CDK 11（细胞周期蛋白依赖性激酶11）基因具有内部核糖体进入位点（IRES），允许两种蛋白激酶的表达。较长的110-kDa亚型在细胞周期中以恒定水平表达，较短的58-kDa亚型仅在G2和M期表达。通过RNA干扰（RNAi），我们发现CDK 11基因是有丝分裂纺锤体形成所必需的。CDK 11 RNAi导致有丝分裂检查点激活。有丝分裂细胞被短纺锤体或单极纺锤体阻滞。γ-微管蛋白以及Plk 1和Aurora A蛋白激酶水平在中心体处大大降低，导致微管成核缺陷。我们发现，有丝分裂的CDK 11 p58亚型，而不是CDK 11 p110亚型，与有丝分裂的中心体和救援的表型产生的CDK 11 RNAi。这项工作首次证明了CDK 11 p58在中心体成熟和双极纺锤体形态发生中的作用。
The CDK11 (cyclin-dependent kinase 11) gene has an internal ribosome entry site ( IRES), allowing the expression of two protein kinases. The longer 110-kDa isoform is expressed at constant levels during the cell cycle and the shorter 58-kDa isoform is expressed only during G2 and M phases. By means of RNA interference (RNAi), we show that the CDK11 gene is required for mitotic spindle formation. CDK11 RNAi leads to mitotic checkpoint activation. Mitotic cells are arrested with short or monopolar spindles. gamma- Tubulin as well as Plk1 and Aurora A protein kinase levels are greatly reduced at centrosomes, resulting in microtubule nucleation defects. We show that the mitotic CDK11p58 isoform, but not the CDK11p110 isoform, associates with mitotic centrosomes and rescues the phenotypes resulting from CDK11 RNAi. This work demonstrates for the first time the role of CDK11p58 in centrosome maturation and bipolar spindle morphogenesis.