The Third People's Hospital of Hangzhou, Zhejiang, China.
Aging (Albany NY). 2021 Nov 27;13(22):24740-24752. doi: 10.18632/aging.203712.
Fam114A1 is a gene closely related to the development of nerve cells, melanocytes, and nerve cells that originate from the neural crest of the embryonic ectoderm. Recent studies showed that Fam114A1 has a role in the occurrence of ankylosing myelitis spondylitis and autoimmune enteritis; still, its cellular function remains poorly understood. In this study, we investigated the effect of Fam114A1 on the biological activity of melanocytes. We found that the expression of Fam114A1 in vitiligo melanocytes (MCV-L, MCV-N, PI3V) was higher than that in normal melanocytes, and the biological function of melanocytes was significantly affected when the Fam114A1 gene was silenced. Inhibition of Fam114A1 increased proliferation, migration, and melanin synthesis proteins, decreased apoptosis, while its overexpression reversed this process. Mechanistically, we discovered that RACK1 is a target protein of Fam114A1 and that RACK1 can be negatively regulated by Fam114A1. Further study showed that Fam114A1 inhibition could not protect melanocytes from apoptosis once the expression of RACK1 protein was silenced. In summary, Fam114A1 is an effective regulatory protein for regulating the function of melanocytes. Inhibition Fam114A1 protects melanocytes from apoptosis through increasing RACK1.
Fam114A1 是一种与神经细胞、黑色素细胞以及源自胚胎外胚层神经嵴的神经细胞发育密切相关的基因。最近的研究表明，Fam114A1 在强直性脊柱炎和自身免疫性肠炎的发生中起作用；然而，其细胞功能仍知之甚少。在这项研究中，我们研究了 Fam114A1 对黑色素细胞生物学活性的影响。我们发现，在白癜风黑素细胞（MCV-L、MCV-N、PI3V）中 Fam114A1 的表达高于正常黑素细胞，当 Fam114A1 基因沉默时，黑色素细胞的生物学功能受到明显影响。抑制 Fam114A1 增加了增殖、迁移和黑色素合成蛋白，减少了凋亡，而其过表达则逆转了这一过程。从机制上讲，我们发现 RACK1 是 Fam114A1 的靶蛋白，并且 Fam114A1 可以负向调节 RACK1。进一步的研究表明，一旦 RACK1 蛋白的表达被沉默， Fam114A1 抑制就不能保护黑色素细胞免于凋亡。总之， Fam114A1 是一种有效的调节蛋白，可调节黑色素细胞的功能。抑制 Fam114A1 通过增加 RACK1 来保护黑色素细胞免于凋亡。
