Cyclin-dependent kinase 5 regulates MAPK/ERK signaling in the skin of mice.

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.