Disease relevance of UBE4B

• Screening for gene mutations in a 500 kb neuroblastoma tumor suppressor candidate region in chromosome 1p; mutation and stage-specific expression in UBE4B/UFD2 [1].
• Specific interaction between HPV-16 E1-E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network [2].
• E1-E4 does not seem to be a component of the virus particle or to be needed for transformation in vitro, but accumulates in the cytoplasm, where in certain benign lesions it can comprise 20-30% of total cell protein [2].
• Identification of an E1A-inducible cellular factor that interacts with regulatory sequences within the adenovirus E4 promoter [3].
• Adenovirus type 9 (Ad9) is distinct among human adenoviruses because it elicits solely mammary tumors in animals and its primary oncogenic determinant is the E4 region-encoded ORF1 (E4-ORF1) protein [4].

Psychiatry related information on UBE4B

• Apolipoprotein (apo) E4 is a major risk factor for Alzheimer's disease, and many studies have suggested that apoE has isoform-specific effects on the deposition or clearance of amyloid beta (Abeta) peptides [5].

High impact information on UBE4B

• The third, E1-E4, is derived primarily from the E4 open reading frame, which represents a region of maximal divergence between different HPV types [2].
• We show here that expression of the HPV-16 E1-E4 protein in human keratinocytes (the natural host cell for HPV infection) results in the total collapse of the cytokeratin matrix [2].
• However, this factor is not involved in E1A induction of several other viral genes, including the E4 gene, since it does not bind to the promoters of these genes [3].
• Furthermore, the activation is maximal by 3 h post-infection, consistent with the kinetics of activation of E4 transcription [3].
• By so doing, we have identified at least seven discrete factor interactions involving the E4 promotor [3].

Chemical compound and disease context of UBE4B

• Binding was not tryptophan synthetase E dependent and was, in general, coincident for the HPV-16 E4 and L1 proteins [6].
• The Adenovirus E4 ORF3 Protein Binds and Reorganizes the TRIM Family Member Transcriptional Intermediary Factor 1 Alpha [7].

Biological context of UBE4B

• Given the data presented here, UBE4B/UFD2 stands out as the strongest candidate NBL tumor suppressor gene in the region at this stage [1].
• Based on the correlation of a nuclear factor binding site with promoter sequences required for ethylene induction, we propose that this in vitro DNA-binding activity may represent a factor that is involved in ethylene-regulated E4 gene expression [8].
• Deletion of E4 promoter sequences to 193 base pairs reduces the level of GUS activity but does not affect ethylene induction [8].
• In transgenic tomato plants a chimeric gene construct containing a 1.4-kilobase E4 promoter fused to a beta-glucuronidase reporter gene is rapidly induced by ethylene in ripening fruit [8].
• Transient expression of E4 promoter-luciferase chimeric gene constructs containing various deletions, introduced into tomato fruit pericarp by particle bombardment, indicates that a positive ethylene-responsive region is localized between nucleotides -161 and -85 relative to the transcription start site [8].

Anatomical context of UBE4B

• Stable expression and secretion of apolipoproteins E3 and E4 in mouse neuroblastoma cells produces differential effects on neurite outgrowth [9].
• Previously, we demonstrated in cultured dorsal root ganglion neurons that, in the presence of beta-migrating very low density lipoproteins (beta-VLDL), apolipoprotein (apo) E4, but not apoE3, suppresses neurite outgrowth [9].
• Evidence of cytopathic effect was absent following infection of nonpermissive cell lines with E1/E4-deleted adenovirus in vitro [10].
• Although the H5ilE4I mutant lacked at least five E4 genes, it was nondefective for growth in HeLa cells [11].
• Using an inducible mammalian expression system, we have shown that 16E1 wedge E4 arrests HeLa cervical epithelial cells in G(2) [12].

Associations of UBE4B with chemical compounds

• Transcription of the E4 gene is controlled by an increase in ethylene concentration during tomato fruit ripening [8].
• Mutagenesis studies revealed a proline-rich region between amino acids 17 and 45 of 16E1 wedge E4 to be important for arrest [12].
• Also, AAV-induced inhibition of E2A and E4 mRNA production did not occur in the presence of hydroxyurea [13].
• The principal metabolite (m/z 686) was derived from glutathione conjugation and side chain elimination, while the minor metabolite gave a protonated molecule (m/z 496) [14].
• Phosphoserine and phosphothreonine were identified in all 16/17K E4 fractions but not phosphotyrosine [15].

Other interactions of UBE4B

• It might be speculated that the proteins generated from UBE4B and UBE4A are involved in protecting the cell from environmental stress and that inactivation of either of them could contribute to malignancy [16].

Analytical, diagnostic and therapeutic context of UBE4B

• Establishment of the 293-E4 cell line and the generation of E1/E4-deleted adenovirus vectors may prolong gene expression in vivo and significantly improve the safety of adenovirus vectors for human gene therapy [10].
• Indirect immunofluorescence assays demonstrated that TIF1alpha is reorganized into track structures that contain PML upon E4 ORF3 expression [7].
• Using immunoelectron microscopy, we have investigated the localization of HPV 16 E4 and L1 proteins in a keratinized epithelium formed by grafting HPV 16-containing cervical keratinocytes onto the athymic mouse [17].
• By Western blotting with this antibody, we detected E4 gene products in six out of 18 condyloma acuminata specimens [18].
• By Southern blot analysis, it was found that C-13 harboured HPV-6 DNA but that C-1 and C-8 harboured HPV-11 DNA, indicating that the E4 proteins of HPV-6 and -11 have cross-reactive antigenicity [18].

References