Department of Pharmacology, University of Arizona, Tucson, AZ 85724, USA.
Oncogene. 2013 Jun 13;32(24):2907-16. doi: 10.1038/onc.2012.350. Epub 2012 Aug 27.
The far upstream binding protein 1 (FBP1) was first identified as a DNA-binding protein that regulates c-Myc gene transcription through binding to the far upstream element (FUSE) in the promoter region 1.5 kb upstream of the transcription start site. FBP1 collaborates with TFIIH and additional transcription factors for optimal transcription of the c-Myc gene. In recent years, mounting evidence suggests that FBP1 acts as an RNA-binding protein and regulates mRNA translation or stability of genes, such as GAP43, p27(Kip) and nucleophosmin. During retroviral infection, FBP1 binds to and mediates replication of RNA from Hepatitis C and Enterovirus 71. As a nuclear protein, FBP1 may translocate to the cytoplasm in apoptotic cells. The interaction of FBP1 with p38/JTV-1 results in FBP1 ubiquitination and degradation by the proteasomes. Transcriptional and post-transcriptional regulations by FBP1 contribute to cell proliferation, migration or cell death. FBP1 association with carcinogenesis has been reported in c-Myc dependent or independent manner. This review summarizes biochemical features of FBP1, its mechanism of action, FBP family members and the involvement of FBP1 in carcinogenesis.
远上游结合蛋白 1（FBP1）最初被鉴定为一种 DNA 结合蛋白，通过与转录起始位点上游 1.5kb 的启动子区域中的远上游元件（FUSE）结合，调节 c-Myc 基因转录。FBP1 与 TFIIH 和其他转录因子合作，以实现 c-Myc 基因的最佳转录。近年来，越来越多的证据表明，FBP1 作为一种 RNA 结合蛋白，调节基因的 mRNA 翻译或稳定性，如 GAP43、p27(Kip)和核仁磷酸蛋白。在逆转录病毒感染过程中，FBP1 结合并介导丙型肝炎病毒和肠道病毒 71 的 RNA 复制。作为一种核蛋白，FBP1 可能在凋亡细胞中转位到细胞质。FBP1 与 p38/JTV-1 的相互作用导致 FBP1 通过蛋白酶体进行泛素化和降解。FBP1 的转录和转录后调节促进细胞增殖、迁移或细胞死亡。FBP1 与致癌作用的关联已在 c-Myc 依赖性或独立性方式下被报道。本综述总结了 FBP1 的生化特征、作用机制、FBP 家族成员以及 FBP1 在致癌作用中的参与情况。
