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

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.

CDKL1 promotes tumor proliferation and invasion in colorectal cancer

“…It can cause G1 cell cycle arrest and produce marked tumor regression in mice bearing human colon carcinoma 24. CDKL1 shares the same functional domains structurally as the CDKs, such as the cdc2 sequence features 3,5. The phylogenetic conservation of this molecule underscores their potential physiological similarity.…”

Knockdown of Cyclin-dependent Kinase 10 (cdk10) Gene Impairs Neural Progenitor Survival via Modulation of raf1a Gene Expression

“…The progressively restricted pattern of cdk10 expression was similar to that of other cdk and cdk-related genes in zebrafish. The cdk7/cyclin H and cdkl1 genes are ubiquitously distributed before gastrulation (14,18). At 24 HPF and thereafter, cdk7 and cyclin H are primarily FIGURE 10.…”

“…expressed in the brain, eye, and heart (14). The expression of cdkl1, which is another cdc2-related protein kinase, is restricted to the floor plate, pronephric ducts, and hypochord at 12 HPF (18). These cdks may exhibit redundant functions during the early developmental stage and perform specific functions during late developmental stages.…”

“…Immunoblot Analysis and in Vitro Kinase Assay-Five hundred micrograms of total cell lysates derived from HEK 293 cells overexpressing GFP alone or the GFP-cdk10 fusion protein was subjected to immunoprecipitation using an anti-GFP antibody, and a kinase assay was performed as described previously (18,21). After washing three times with kinase buffer (25 mM Tris, pH 7.5, 150 mM NaCl, 2 mM dithiothreitol, and 0.1 mM sodium orthovanadate), the precipitates were incubated with H1 histone in kinase buffer supplemented with 0.1 mM ATP, pH 7.0, 5 Ci of [␥-32 P]ATP, and 10 mM MgCl 2 at 37°C for 10 min.…”

“…Recently, cdkl1 was reported to fulfill a function in zebrafish development. Interruption of cdkl1 expression decreases neurogenin-1 (ngn1) levels in the brain and sonic hedgehog expression in the floor plate region (18). In the present study, we used zebrafish as an animal model to investigate the developmental role of cdk10.…”