Far upstream element binding protein 1: a commander of transcription, translation and beyond

Abstract

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, p27Kip 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.

Interactions between SAP155 and FUSE-Binding Protein-Interacting Repressor Bridges c-Myc and P27Kip1 Expression

“…4,15); therefore, P89 expression should be critical for c-myc regulation through FIR (4,16). This study revealed that both total FIRs (authentic FIR and FIR splicing variants including FIRDexon2) and P89 expression were significantly activated in colorectal cancer tissues (T) compared with corresponding nontumor tissues (N; Fig.…”

“…6B). At this point, c-myc expression should be tightly constrained when cells respond to certain stimulations (16).…”

Far Upstream Element-Binding Protein 1 Binds the 3′ Untranslated Region of PKD2 and Suppresses Its Translation

“…42 FUBP1 promotes cell proliferation, survival and metastasis through up-regulating c-Myc and plays important roles in organ development, including lung, brain, and neural network development. 27,43,44 In contrast, FUBP1 was known to transcriptionally downregulate the expression of TNFa. 45 Interestingly, c-Myc is elevated in cystic tissues of various PKD models and TNFa is elevated in PKD2 +/2 mice.…”

“…It was known that, under normal physiologic conditions, FUBP1 primarily localizes in the nucleus, and that under stress conditions, such as in the presence of heat shock, viral infection, and oxidative stress, FUBP1 either stops entering the nucleus or translocates from the nucleus to the cytoplasm, resulting in cytoplasmic accumulation. 27 Interestingly, TGF-b1, which is upregulated in ADPKD, was also reported to induce translocation of FUBP1 from the nucleus to the cytoplasm. 58 The presence of a physical interaction between FUBP1 and eIF4E-binding protein 4EBP1 suggests the complex 3FI-FUBP1 located at the 39UTR of PKD2 mRNA is indeed connected, via 4EBP1, to the initiation complex located at the 59UTR of PKD2 mRNA.…”

“…FUBP1 was previously reported to bind AU-rich regions of RNAs through a signature sequence of AUUUA. 27 Indeed, human 3FI contains 68% AU and 3FI from six different species all contain one to three AUUUA sequences (Supplemental Figure 1). Taken together, these results show a specific effect of FUBP1 on PKD2 translation but not on its mRNA stability, and suggest that FUBP1 may have mediated, at least in part, our observed inhibitory effect of 3FI.…”