Zebrafish Cyclin-Dependent Protein Kinase–Like 1 (zcdkl1): Identification and Functional Characterization

Li-Sung Hsu,Chi-Wei Yeh,Chen-Yuan Tseng,Cyong-Jhih Liang,Jen-Ning Tsai

doi:10.3390/ijms12063606

Abstract

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.

Highlights

IntroductionThe cyclin-dependent protein kinase (CDK) protein family, a group of serine/threonine kinases, has been demonstrated to be an important regulator of cell division at the G1/S and G2/M checkpoints [1].Progression of the cell cycle depends on the association of CDK with a specific cyclin to form active complexes, which control the expression of downstream genes involved in the cell cycle [1].Interaction of cdc (CDK1) with cyclin A mediates the transition of the G2/M phase, whereas activation of cdc after interaction with cyclin B is the key step that triggers mitosis [2,3].A family of protein kinases called cdc2-related kinase, which include CDK10, PCTAIRE, cyclin-dependent protein kinase-like 1 (CDKL1), CDKL2, and CDKL3, was recently identified through the biochemical and genetic approach; they are named based on the sequence corresponding to the PSTAIRE motif of cdc2 [4]
Our results indicate that knockdown of zcdkl1 caused abnormalities in zebrafish development that can be apparently recovered by co-injection of zcdkl1 mRNA
Down-regulation of zcdkl1 led to decreased ngn-1 and shh expression in the floor plate, which can be rescued by co-injection with zcdkl1 mRNA

Summary

Introduction

The cyclin-dependent protein kinase (CDK) protein family, a group of serine/threonine kinases, has been demonstrated to be an important regulator of cell division at the G1/S and G2/M checkpoints [1].Progression of the cell cycle depends on the association of CDK with a specific cyclin to form active complexes, which control the expression of downstream genes involved in the cell cycle [1].Interaction of cdc (CDK1) with cyclin A mediates the transition of the G2/M phase, whereas activation of cdc after interaction with cyclin B is the key step that triggers mitosis [2,3].A family of protein kinases called cdc2-related kinase, which include CDK10, PCTAIRE, CDKL1, CDKL2, and CDKL3, was recently identified through the biochemical and genetic approach; they are named based on the sequence corresponding to the PSTAIRE motif of cdc2 [4]. The cyclin-dependent protein kinase (CDK) protein family, a group of serine/threonine kinases, has been demonstrated to be an important regulator of cell division at the G1/S and G2/M checkpoints [1]. Progression of the cell cycle depends on the association of CDK with a specific cyclin to form active complexes, which control the expression of downstream genes involved in the cell cycle [1]. Interaction of cdc (CDK1) with cyclin A mediates the transition of the G2/M phase, whereas activation of cdc after interaction with cyclin B is the key step that triggers mitosis [2,3]. A family of protein kinases called cdc2-related kinase, which include CDK10, PCTAIRE, CDKL1, CDKL2, and CDKL3, was recently identified through the biochemical and genetic approach; they are named based on the sequence corresponding to the PSTAIRE motif of cdc2 [4].

Results

Discussion

Conclusion