Hsu Li-Sung, Liang Cyong-Jhih, Tseng Chen-Yuan, Yeh Chi-Wei, Tsai Jen-Ning
Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan; E-Mails:
Int J Mol Sci. 2011;12(6):3606-17. doi: 10.3390/ijms12063606. Epub 2011 Jun 3.
The cyclin-dependent protein kinase family regulates a wide range of cellular functions such as cell cycle progression, differentiation, and apoptosis. In this study, we identified a zebrafish cyclin-dependent protein kinase-like 1 protein called zebrafish cdkl1 (zcdkl1), which shared a high degree of homology and conserved synteny with mammalian orthologs. zcdkl1 exhibited abilities for phosphorylation of myelin basic protein and histone H1. RT-PCR analysis revealed that zcdkl1 was expressed starting from fertilization and continuing thereafter. In adult tissues, zcdkl1 was predominantly detected in brain, ovary, and testis, and was expressed at low levels in other tissues. At 50% epiboly stage, zcdkl1 was widely expressed. At 12 to 48 h post-fertilization, zcdkl1 was predominantly expressed in the hypochord, the medial and lateral floor plate, and the pronephric duct. Interference of zcdkl1 expression resulted in abnormalities, such as brain and eye malformation, pericardial edema, and body axis curvature. Disruption of zcdkl1 reduced neurogenin-1 in the brain and sonic hedgehog expression in the floor plate region. These deformities were apparently rescued by co-injection of zcdkl1 mRNA. Findings of this study indicate that zcdkl1 plays an essential role in zebrafish development.
细胞周期蛋白依赖性蛋白激酶家族调节多种细胞功能，如细胞周期进程、分化和凋亡。在本研究中，我们鉴定出一种斑马鱼细胞周期蛋白依赖性蛋白激酶样1蛋白，称为斑马鱼cdkl1（zcdkl1），它与哺乳动物直系同源物具有高度的同源性和保守的同线性。zcdkl1表现出对髓鞘碱性蛋白和组蛋白H1进行磷酸化的能力。逆转录聚合酶链反应分析显示，zcdkl1从受精开始表达，并在之后持续表达。在成体组织中，zcdkl1主要在脑、卵巢和睾丸中检测到，而在其他组织中表达水平较低。在囊胚期50%时，zcdkl1广泛表达。在受精后12至48小时，zcdkl1主要在脊索、内侧和外侧底板以及前肾管中表达。zcdkl1表达的干扰导致异常，如脑和眼畸形、心包水肿和体轴弯曲。zcdkl1的破坏降低了脑中神经生成素-1和底板区域中声波刺猬因子的表达。通过共注射zcdkl1 mRNA，这些畸形明显得到挽救。本研究结果表明，zcdkl1在斑马鱼发育中起重要作用。
