The State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, China.
J Cell Mol Med. 2012 May;16(5):1134-45. doi: 10.1111/j.1582-4934.2011.01388.x.
Zinc finger proteins (ZNF) play important roles in various physiological processes. Here we report that ZNF300, a novel zinc finger protein, identified specifically in humans, promotes tumour development by modulating the NF-κB pathway. Inflammatory factors were found to induce ZNF300 expression in HeLa cell line, and ZNF300 expression further enhanced NF-κB signalling by activating TRAF2 and physically interacting with IKKβ. Furthermore, ZNF300 overexpression increased ERK1/2 phosphorylation and the expression of c-myc, IL-6, and IL-8 but decreased the expression of p21(waf-1) and p27(Kip1) ; whose down-regulation led to the opposite effect. Most importantly, ZNF300 overexpression stimulated cancer cell proliferation in vitro and significantly enhanced tumour development and metastasis in mouse xenograft model, while knocking down ZNF300 led to the opposite effects. We have identified a novel function for ZNF300 in tumour development that may uniquely link inflammation and NF-κB to tumourigenesis in humans but not in mice.
锌指蛋白（ZNF）在各种生理过程中发挥重要作用。在这里，我们报告了一种新的锌指蛋白 ZNF300，它是人类特有的，通过调节 NF-κB 通路促进肿瘤的发展。在 HeLa 细胞系中发现炎症因子诱导 ZNF300 的表达，并且 ZNF300 通过激活 TRAF2 和与 IKKβ 物理相互作用进一步增强 NF-κB 信号。此外，ZNF300 的过表达增加了 ERK1/2 磷酸化和 c-myc、IL-6 和 IL-8 的表达，但降低了 p21(waf-1) 和 p27(Kip1) 的表达；其下调导致相反的效果。最重要的是，ZNF300 的过表达在体外刺激癌细胞增殖，并显著增强了小鼠异种移植模型中的肿瘤发展和转移，而敲低 ZNF300 则产生相反的效果。我们已经确定了 ZNF300 在肿瘤发展中的一个新功能，它可能将炎症和 NF-κB 与人类而不是小鼠的肿瘤发生独特地联系起来。
