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首页> 外文期刊>Cellular Physiology and Biochemistry >Eukaryotic Translation Initiator Protein 1A Isoform, CCS-3, Enhances the Transcriptional Repression of p21CIP1 by Proto-oncogene FBI-1 (Pokemon/ZBTB7A)
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Eukaryotic Translation Initiator Protein 1A Isoform, CCS-3, Enhances the Transcriptional Repression of p21CIP1 by Proto-oncogene FBI-1 (Pokemon/ZBTB7A)

机译：真核翻译起始蛋白1A亚型，CCS-3，增强原癌基因FBI-1（Pokemon / ZBTB7A）对p21CIP1的转录抑制。

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摘要

FBI-1, a member of the POK (POZ and Kruppel) family of transcription factors, plays a role in differentiation, oncogenesis, and adipogenesis. eEF1A is a eukaryotic translation elongation factor involved in several cellular processes including embryogenesis, oncogenic transformation, cell proliferation, and cytoskeletal organization. CCS-3, a potential cervical cancer suppressor, is an isoform of eEF1A. We found that eEF1A forms a complex with FBI-1 by co-immunoprecipitation, SDS-PAGE, and MALDI-TOF Mass analysis of the immunoprecipitate. GST fusion protein pull-downs showed that FBI-1 directly interacts with eEF1A and CCS-3 via the zinc finger and POZ-domain of FBI-1. FBI-1 co-localizes with either eEF1A or CCS-3 at the nuclear periplasm. CCS-3 enhances transcriptional repression of the p21CIP1 gene (hereafter referred to as p21) by FBI-1. The POZ-domain of FBI-1 interacts with the co-repressors, SMRT and BCoR. We found that CCS-3 also interacts with the co-repressors independently. The molecular interaction between the co-repressors and CCS-3 at the POZ-domain of FBI-1 appears to enhance FBI-1 mediated transcriptional repression. Our data suggest that CCS-3 may be important in cell differentiation, tumorigenesis, and oncogenesis by interacting with the proto-oncogene FBI-1 and transcriptional co-repressors.
机译：FBI-1是POK（POZ和Kruppel）转录因子家族的成员，在分化，肿瘤发生和脂肪形成中起作用。 eEF1A是一种真核翻译延伸因子，涉及几个细胞过程，包括胚胎发生，致癌转化，细胞增殖和细胞骨架组织。 CCS-3是一种潜在的宫颈癌抑制剂，是eEF1A的同工型。通过共免疫沉淀，SDS-PAGE和MALDI-TOF免疫沉淀的质量分析，我们发现eEF1A与FBI-1形成复合物。 GST融合蛋白的下拉显示，FBI-1通过锌指和FBI-1的POZ域直接与eEF1A和CCS-3相互作用。 FBI-1与eEF1A或CCS-3共定位在核周质上。 CCS-3增强了FBI-1对p21CIP1基因（以下称为p21）的转录抑制。 FBI-1的POZ域与共抑制子SMRT和BCoR相互作用。我们发现CCS-3也独立地与辅助阻遏物相互作用。在FBI-1的POZ域中，共抑制子和CCS-3之间的分子相互作用似乎增强了FBI-1介导的转录抑制。我们的数据表明，CCS-3通过与原癌基因FBI-1和转录共阻遏物相互作用，可能在细胞分化，肿瘤发生和肿瘤发生中起重要作用。

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