College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, China.
Laboratory of Animal Biotechnology and Genomics, Division of Animal and Nutritional Sciences, West Virginia University, Morgantown, WV, 26506, USA.
Sci Rep. 2017 Oct 23;7(1):13783. doi: 10.1038/s41598-017-12567-1.
The mammalian integumentary system plays important roles in body homeostasis, and dysfunction of melanogenesis or epidermal development may lead to a variety of skin diseases, including melanoma. Skin pigmentation in humans and coat color in fleece-producing animals are regulated by many genes. Among them, microphthalmia-associated transcription factor (MITF) and paired-box 3 (PAX3) are at the top of the cascade and regulate activities of many important melanogenic enzymes. Here, we report for the first time that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of MITF and PAX3. Cdk5 knockdown in mice causes a lightened coat color, a polarized distribution of melanin and hyperproliferation of basal keratinocytes. Reduced expression of Keratin 10 (K10) resulting from Cdk5 knockdown may be responsible for an abnormal epidermal structure. In contrast, overexpression of Cdk5 in sheep (Ovis aries) only produces brown patches on a white background, with no other observable abnormalities. Collectively, our findings show that Cdk5 has an important functional role in the regulation of melanin production and transportation and in normal development of the integumentary system.
哺乳动物的表皮系统在维持身体内环境稳定方面发挥着重要作用，而黑色素生成或表皮发育的功能障碍可能导致多种皮肤疾病，包括黑色素瘤。人类的皮肤色素沉着和产绒动物的毛色由许多基因调控。其中，小眼畸形相关转录因子（MITF）和配对盒基因 3（PAX3）位于级联反应的顶端，调节许多重要的黑色素生成酶的活性。在这里，我们首次报道细胞周期蛋白依赖性激酶 5（Cdk5）是 MITF 和 PAX3 的重要调节因子。Cdk5 在小鼠中的敲低导致毛色变浅、黑色素的极化分布和基底角质形成细胞的过度增殖。Cdk5 敲低导致 Keratin 10（K10）表达减少，可能是表皮结构异常的原因。相比之下，绵羊（Ovis aries）中 Cdk5 的过表达仅在白色背景上产生棕色斑块，没有其他可观察到的异常。总的来说，我们的研究结果表明，Cdk5 在黑色素生成和运输的调节以及表皮系统的正常发育中具有重要的功能作用。
