Liu Xuexian, Zhang Pengqian, Ji Kaiyuan, Zhang Junzhen, Yang Shanshan, Du Bin, Hu Shuaipeng, Fan Ruiwen
College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Mingxian South Road, Taigu 030801, China.
Department of Ecology Research, Beijing Milu Ecological Research Center, Nanhaizi, Daxing District, Beijing 102600, China.
Acta Histochem. 2018 Jan;120(1):15-21. doi: 10.1016/j.acthis.2017.10.009. Epub 2017 Nov 11.
Cyclin-dependent kinase 5 (CDK5) is a proline-directed serine/threonine kinase that has been shown to play important roles in many tissues except the nervous system. We previously reported that CDK5 showed differential expression in the transcriptome profiles of the skin of alpacas with different hair colors. To understand the functional role of CDK5 in hair color determination, we constructed CDK5-knockdown mice and identified the effect on the mitogen-activated protein kinase (MAPK) pathway in the mouse skin. Quantitative real-time polymerase chain reaction, co-immunoprecipitation, and western blotting were performed to analyze the effects of CDK5-knockdown on the MAPK pathway in mice. The results showed that MAP3K6 was inhibited by phosphorylated CDK5 through its activator CDK7. The decrease in MAP3K6 levels caused down-regulation of MEK1 and ERK expression, leading to the up-regulation of miR-143-3p, which targets MAP3K6 via Dicer. Taken together, our findings indicate that CDK5 functions in regulating the MAPK pathway. Given that MAP3K6 was inhibited in two directions, this mechanism can provide insight into the contributions of the MAPK/ERK pathway to the inhibition of melanin production.
细胞周期蛋白依赖性激酶5（CDK5）是一种脯氨酸导向的丝氨酸/苏氨酸激酶，已被证明在除神经系统外的许多组织中发挥重要作用。我们之前报道过，CDK5在不同毛色羊驼皮肤的转录组图谱中表现出差异表达。为了了解CDK5在毛色决定中的功能作用，我们构建了CDK5基因敲低小鼠，并确定其对小鼠皮肤中丝裂原活化蛋白激酶（MAPK）通路的影响。通过定量实时聚合酶链反应、免疫共沉淀和蛋白质印迹法来分析CDK5基因敲低对小鼠MAPK通路的影响。结果表明，磷酸化的CDK5通过其激活剂CDK7抑制MAP3K6。MAP3K6水平的降低导致MEK1和ERK表达下调，进而导致miR-143-3p上调，miR-143-3p通过Dicer靶向MAP3K6。综上所述，我们的研究结果表明CDK5在调节MAPK通路中发挥作用。鉴于MAP3K6在两个方向上受到抑制，这一机制可以为MAPK/ERK通路对黑色素生成抑制的贡献提供见解。
