Williams M, Lyu M S, Yang Y L, Lin E P, Dunbrack R, Birren B, Cunningham J, Hunter K
Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
Genomics. 1999 Feb 1;55(3):327-34. doi: 10.1006/geno.1998.5679.
We describe here a novel member of the slow-kinetics immediate-early gene family. Ier5 is an intronless gene, encoding a serum- and growth factor-inducible message of 2123 nucleotides that is present in a wide variety of tissues. The predicted open reading frame encodes a 308-amino-acid, highly proline-rich protein with homology to the amino terminus of the immediate-early gene pip92/Ier2/ETR101. Ier5 is predicted to be a nuclear protein and contains a PEST-like sequence, suggesting rapid protein degradation. Multiple phosphorylation sites are present. Ier5 shows growth factor induction kinetics similar to that of pip92/Ier2/ETR101, but unlike pip92/Ier2/ETR101 does not appear to require phosphokinase C activity for transcriptional activation. The sequence of the promoter region of Ier5 was determined and examined for transcription factor binding sites thought to mediate serum and growth factor response. Multiple AP-1 sites and an Ets-1 site were observed, but the CArG and CArG-like boxes of the serum response element were absent. The predicted nuclear localization of Ier5, coupled with the potential for rapid regulation by phosphorylation and/or degradation, suggests that Ier5 may play an important role in mediating the cellular response to mitogenic signals.
我们在此描述慢动力学即刻早期基因家族的一个新成员。Ier5是一个无内含子基因，编码一个2123个核苷酸的血清和生长因子诱导型信息，存在于多种组织中。预测的开放阅读框编码一个308个氨基酸、富含脯氨酸的蛋白质，与即刻早期基因pip92/Ier2/ETR101的氨基末端具有同源性。Ier5预计是一种核蛋白，并含有一个类似PEST的序列，提示蛋白质快速降解。存在多个磷酸化位点。Ier5显示出与pip92/Ier2/ETR101相似的生长因子诱导动力学，但与pip92/Ier2/ETR101不同的是，其转录激活似乎不需要磷酸激酶C活性。确定了Ier5启动子区域的序列，并检查了被认为介导血清和生长因子反应的转录因子结合位点。观察到多个AP-1位点和一个Ets-1位点，但血清反应元件的CArG和类CArG框不存在。Ier5预测的核定位，加上通过磷酸化和/或降解进行快速调节的可能性，表明Ier5可能在介导细胞对有丝分裂信号的反应中起重要作用。
