Department of Clinical Laboratory, the First People's Hospital in Jiangbei District, Chongqing 400020, China.
Mol Biol Rep. 2012 Feb;39(2):873-9. doi: 10.1007/s11033-011-0811-5. Epub 2011 May 15.
As a highly conserved nuclear protein, death domain-associated protein (Daxx) plays an important role in transcriptional control, carcinogenesis, and resistance to virus infection and so on. In order to further investigate the mechanism of Daxx, the yeast two-hybrid technique was used to screen the intra-cellular proteins interacting with Daxx. And 13 positive colonies and three proteins interacting with Daxx were obtained. One of the candidate proteins was identified as ferritin, heavy polypeptide 1(FTH1). The interaction between Daxx and FTH1 was further supported by GST pull-down and co-immunoprecipitation respectively. Then Daxx was determined to induce apoptosis and FTH1 can inhibit Daxx-mediated apoptosis. Besides, it is found that Daxx mediated apoptosis through the Fas-Daxx-ASK1-JNK1 signaling pathway, while FTH1 can inhibit the activation of JNK signaling pathway. We present evidence to demonstrate the FTH1 and Daxx are able to participate in apoptosis pathway through JNK signal molecule and FTH1 can inhibit this pathway.
作为一种高度保守的核蛋白，死亡结构域相关蛋白（Daxx）在转录调控、致癌作用以及抵抗病毒感染等方面发挥着重要作用。为了进一步研究 Daxx 的作用机制，我们利用酵母双杂交技术筛选与 Daxx 相互作用的细胞内蛋白，得到了 13 个阳性克隆和 3 种与 Daxx 相互作用的蛋白。其中一个候选蛋白被鉴定为铁蛋白重链 1（FTH1）。GST 下拉和免疫共沉淀实验进一步证实了 Daxx 和 FTH1 之间的相互作用。随后发现 Daxx 能够诱导细胞凋亡，而 FTH1 可以抑制 Daxx 介导的细胞凋亡。此外，我们还发现 Daxx 通过 Fas-Daxx-ASK1-JNK1 信号通路诱导细胞凋亡，而 FTH1 可以抑制 JNK 信号通路的激活。本研究为 FTH1 和 Daxx 通过 JNK 信号分子参与细胞凋亡途径提供了证据，并且证明 FTH1 可以抑制该途径。
