Proteins encoded by immediate-early response (IER) family genes, IER2, IER5, and IER5L, share homology at their N-terminal regions. IER5 binds to protein phosphatase 2A (PP2A) and enhances dephosphorylation of PP2A target proteins such as heat shock factor HSF1. Here, we show the expression of IER family genes and the target protein-specific function of IER proteins. The IER homology regions of IER2 and IER5L are required for the interaction with PP2A. Expression of IER2 and IER5L in cells leads to reduced phosphorylation of HSF1 and derepression of its transcriptional activity. Although IER5 and IER5L enhance dephosphorylation of ribosomal protein S6 kinase, IER2 fails to do so. IER2, IER5, and IER5L all bind to the cell cycle regulator CDC25A and convert it to the hypophosphorylated form, which causes dissociation from 14‐3-3 regulatory protein. IER5 differentially regulates CDC25A levels in cells under normal and thermal stress conditions. These results suggest that IER proteins are target protein-specific regulators of PP2A activity and modulate cell proliferation through CDC25A activity.

立即反应（IER）家族基因IER2，IER5和IER5L编码的蛋白质在它们的N-末端区域具有同源性。IER5与蛋白质磷酸酶2A（PP2A）结合，并增强PP2A目标蛋白（如热激因子HSF1）的去磷酸化。在这里，我们显示IER家族基因的表达和IER蛋白的目标蛋白特异性功能。与PP2A相互作用需要IER2和IER5L的IER同源区域。IER2和IER5L在细胞中的表达导致HSF1磷酸化水平降低和其转录活性降低。尽管IER5和IER5L增强了核糖体蛋白S6激酶的去磷酸化作用，但IER2却没有这样做。IER2，IER5和IER5L均与细胞周期调节剂CDC25A结合，并将其转化为次磷酸化形式，从而导致与14-3-3调节蛋白解离。IER5在正常和热应激条件下差异调节细胞中CDC25A的水平。这些结果表明，IER蛋白是PP2A活性的靶蛋白特异性调节剂，并通过CDC25A活性调节细胞增殖。