Disease relevance of FUBP1

• Because transcriptionally generated torsion melts FUSE in vitro even in linear DNA, and FBP/FBP Interacting Repressor (FIR) regulates transcription through TFIIH, these components have been speculated to be the mechanosensor (FUSE) and effectors (FBP/FIR) of a real-time mechanism controlling c-myc transcription [1].
• Therefore, we wondered whether far upstream element-binding protein 1 levels are altered in the absence of Parkin and in Parkinson disease [2].
• We herein report that far upstream element-binding protein 1 accumulates in Parkin knock-out mice, patients with autosomal recessive juvenile parkinsonism, sporadic Parkinson disease, and diffuse Lewy Body disease as well as the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease [2].
• The kinetic results are consistent with the participation of this conserved residue or position in the protonation of the carbinolamine intermediate and dehydration of the Schiff base in FBP aldolase and, by analogy, the class I aldolase family [3].
• The degree of expression of FBP binding sites in the primary cancerous region correlated with the occurrence of lymph node metastasis [4].

Psychiatry related information on FUBP1

• The lowered folate binding capacity of FBP is not explained by a defect of the FBP1 or FBP2 gene, but most likely occurs as a secondary phenomenon in Rett syndrome [5].

High impact information on FUBP1

• FBP bound to FUSE acts through TFIIH at the promoter [6].
• The KH domains of the FUSE-binding protein (FBP), a regulator of c-myc expression, bind in vivo and in vitro to the single-stranded far-upstream element (FUSE), 1,500 base pairs upstream from the c-myc promoter [6].
• Deletion and insertion mutagenesis of FBP defined a novel single-strand DNA-binding domain [7].
• To determine whether the FUSE site, in vivo, possesses single-strand conformation, and therefore could be bound by FBP, cells were treated with potassium permanganate (KMnO4) to modify unpaired bases [7].
• Transfection of FBP into human leukemia cells stimulated c-myc-promoter-driven expression from a reporter plasmid in a FUSE-dependent manner [7].

Biological context of FUBP1

• FUSE binding protein (FBP) binds in vivo and in vitro with the single-stranded far upstream element (FUSE) upstream of the c-myc gene [8].
• FUSE-binding protein (FBP) binds the single-stranded far upstream element of active c-myc genes, possesses potent transcription activation and repression domains, and is necessary for c-myc expression [9].
• FarUpStream Element (FUSE) Binding Protein (FBP) binds the human c-myc FUSE in vitro only in single-stranded or supercoiled DNA [1].
• To ascertain whether the FUSE/FBP/FIR system operates according to this hypothesis in vivo, the flux of activators, repressors and chromatin remodeling complexes on the c-myc promoter was monitored throughout the serum-induced pulse of transcription [1].
• Comparison with GenBank sequences revealed a fourth FBP family member encoded by Caenorhabditis elegans chromosome III, illustrating the high degree of homology in this evolutionarily ancient and conserved family [10].

Anatomical context of FUBP1

• Using a strand-displacement assay with 32P labeled oligonucleotide annealed to M13 ssDNA we have purified to apparent homogeneity and characterized a novel DNA unwinding enzyme from HeLa cell nuclei, human DNA helicase V (HDH V) [11].
• In fibroblasts, the coordinate expression of FBP and c-myc throughout all phases of the cell cycle is consistent with FBP's role as a growth-dependent regulator of c-myc expression [12].
• In concert with a loss of c-myc expression, both FUSE binding protein (FBP) mRNA and protein levels disappeared in HL60 cells after PMA-induced differentiation, due to a drop in the rate of transcription that was measured by nuclear runoff [12].
• When T cells and fibroblasts were stimulated to transit from G0 into the cell cycle, there was a dramatic rise of both FBP mRNA and DNA sequence specific nuclear FBP binding activity, which correlated with the appearance of c-myc mRNA [12].
• All metastatic lymph nodes strongly reacted with FBP [4].

Associations of FUBP1 with chemical compounds

• Upon treatment with the transcription inhibitor actinomycin D, FBP completely re-localized into dots, but did not exit from the nucleus [8].
• Partial amino acid sequencing revealed that one of the RNA binding proteins coincides with FBP (far upstream element binding protein), previously characterized as a protein that resembles hnRNP K and which binds to a single-stranded, pyrimidine-rich DNA sequence upstream of the c -myc gene to activate its expression [13].
• Identification of far upstream element-binding protein-1 as an authentic Parkin substrate [2].
• Glutaraldehyde- or formalin-fixed intact and trypsinized BSF gave results similar to those obtained with living cells and SBA, WGA, and FBP [14].
• Binding of FBP to the sensor surface could be blocked at concentrations as high as 1 microM with a 100-fold excess of folic acid, indicating the specificity of the folate-FBP interaction and the absence of nonspecific binding to the functionalized surface [15].

Physical interactions of FUBP1

• Moreover, Parkin interacts with and ubiquitinates far upstream element-binding protein 1 facilitating its degradation through the ubiquitin proteasome system [2].

Co-localisations of FUBP1

• Furthermore, FBP co-localized with transcription sites and with the general transcription factor TFIIH, but not with the splicing factor SC-35 [8].

Other interactions of FUBP1

• In addition to its transcriptional role, FBP and its closely related siblings FBP2 (KSRP) and FBP3 have been reported to bind RNA and participate in various steps of RNA processing, transport or catabolism [8].

Analytical, diagnostic and therapeutic context of FUBP1

• The M:(r) determined by SDS-PAGE (66 kDa) corresponds to that measured under native conditions, suggesting that HDH V exists as a monomer in the nucleus [16].
• Gel shift analyses using full length FBP and a related transcription factor confirm that a small-molecule lead compound inhibits DNA binding in a specific manner [17].
• In this report, we describe the development of a quartz crystal microbalance biosensor for detection of folate binding protein (FBP) [15].
• The role of the acid/base residue was probed by site-directed mutagenesis and steady-state and pre-steady-state kinetics on a representative member of this family, FBP aldolase [3].
• Comparison of the fibrin-binding affinities of proteolytic FBPs from the N-terminus (25.9 kDa FBP), the C-terminus (14.4 kDa) and intact Fn by ELISA yielded estimated Kd values of 216, 18 and 2.1 nM, respectively [18].

References