Dept of Cell Biochemistry, Jagiellonian University, Krakow, Poland.
BMC Mol Biol. 2010 Feb 6;11:14. doi: 10.1186/1471-2199-11-14.
MCPIP is a novel CCCH zinc finger protein described as an RNase engaged in the regulation of immune responses. The regulation of expression of the gene coding for MCPIP - ZC3H12A is poorly explored.
Here we report that the proinflammatory cytokine IL-1beta rapidly induces the synthesis of MCPIP in primary monocyte-derived macrophages and HepG2 cells. This up-regulation takes place through the MAP kinase pathway and following activation of the transcription factor Elk-1. Using a ZC3H12A reporter construct we have shown that a ZC3H12A promoter region, stretching from -76 to +60, mediates activation by IL-1beta. This region contains binding sites for Elk-1 and its partner SRF. Chromatin immunoprecipitation analysis confirms in vivo binding of both transcription factors to this region of the ZC3H12A promoter.
We conclude that the transcription factor Elk-1 plays an important role in the activation of ZC3H12A expression in response to IL-1beta stimulation.
MCPIP 是一种新型的 CCCH 锌指蛋白,被描述为一种参与免疫反应调节的 RNA 酶。编码 MCPIP-ZC3H12A 的基因表达的调控还没有得到充分的研究。
在这里,我们报告说,促炎细胞因子 IL-1β 能迅速诱导原代单核细胞衍生的巨噬细胞和 HepG2 细胞中 MCPIP 的合成。这种上调是通过 MAP 激酶途径和转录因子 Elk-1 的激活来实现的。使用 ZC3H12A 报告基因构建体,我们已经表明,一个从 -76 到 +60 的 ZC3H12A 启动子区域介导了 IL-1β 的激活。这个区域包含 Elk-1 及其伙伴 SRF 的结合位点。染色质免疫沉淀分析证实了这两种转录因子在体内与 ZC3H12A 启动子的这一区域的结合。
我们得出结论,转录因子 Elk-1 在 IL-1β 刺激下 ZC3H12A 表达的激活中起着重要作用。