Disease relevance of UBE4A

• The UBE4A gene has been mapped on the human chromosome region 11q23.3, a critical region involved in some specific cancers such as neuroblastoma [1].
• However, in adenovirus-infected cells, E2F is complexed to the 19 kDa product of the adenovirus E4 gene [2].
• Phosphorylation of E2F-1 modulates its interaction with the retinoblastoma gene product and the adenoviral E4 19 kDa protein [2].
• Using the purified fusion proteins as immunogens we raised antisera against the proteins encoded by the ORF E6, E7 and E1 of HPV 18 as well as those encoded by the ORF E6, E7, E4 and L1 of HPV 16 [3].
• To determine whether apoE influences the neurotoxic actions of beta-amyloid (Abeta), we examined the effect of native preparations of apoE3 and E4 on Abeta-induced toxicity in primary cultures of rat hippocampal pyramidal neurons [4].

Psychiatry related information on UBE4A

• Although apolipoprotein (apo) E4 is present in amyloid plaques and neurofibrillary tangles, its pathogenic role in Alzheimer's disease (AD) is unclear [5].
• A population-based study of tau protein and ubiquitin in cerebrospinal fluid in 85-year-olds: relation to severity of dementia and cerebral atrophy, but not to the apolipoprotein E4 allele [6].

High impact information on UBE4A

• In yeast, E4 activity is linked to cell survival under stress conditions, indicating that eukaryotes utilize E4-dependent proteolysis pathways for multiple cellular functions [7].
• The cAMP-responsive cell line S49 was infected with wild-type adenovirus and found to contain elevated levels of mRNAs encoded by all early genes tested (E4, E1A, and E1B), following treatment with dibutyryl cAMP [8].
• Taken together, these results indicate that CHIP is a mammalian E4-like molecule that positively regulates Parkin E3 activity [9].
• Nuclear export of the E1B 55-kDa and E4 34-kDa adenoviral oncoproteins mediated by a rev-like signal sequence [10].
• The 17 kd E4 polypeptide appears to be the product of a spliced mRNA encoding five amino acids from open reading frame (ORF) E1 joined onto 120 from the E4 ORF [11].

Chemical compound and disease context of UBE4A

• An essential oncogenic determinant of subgroup D human adenovirus type 9 (Ad9), which uniquely elicits estrogen-dependent mammary tumors in rats, is encoded by early region 4 open reading frame 1 (E4 ORF1) [12].
• The Adenovirus E4 ORF3 Protein Binds and Reorganizes the TRIM Family Member Transcriptional Intermediary Factor 1 Alpha [13].
• We demonstrate the strong binding of two herpesvirus polypeptides, the human adenovirus protease, vaccinia virus polymerase, human papillomavirus E4 protein, yam mosaic virus polyprotein, human respiratory syncytial virus attachment glycoprotein, human coxsackievirus capsid protein and the product of the AMV179 gene of an insect poxvirus to LC8 [14].

Biological context of UBE4A

• In the liver, the nucleus of similar cells appeared to be unstained or stained at different levels suggesting that UBE4A may have a cell cycle dependent expression or a role of in cell cycle control [1].
• The coding exons of UBE4A were therefore sequenced [15].
• Biochemical factors, including the increased frequency of the apo E-2 phenotype and the decreased frequency of the apo E-4 phenotype, are more important [16].
• Ufd2 is regulated by phosphorylation in mitosis [17].
• Inhibition of Ufd2 expression results in mitotic arrest at the metaphase-anaphase transition, where cells manifest abnormal chromosome morphology, missegregated chromosomes, irregular spindles, and premature separation of sister chromatids [17].

Anatomical context of UBE4A

• UBE4A was present in the skeletal muscle, kidney and liver; a faint band was visible in peripheral blood leukocytes and spleen [1].
• Thirty days post-lesion, hE4 mice had more reactive astrocytes as well as a defective outward migration pattern of the astrocytes in the dentate gyrus [18].
• Although the mechanisms initiating these events are unclear, the antiapoptoic signal requires the presence of E4 genes in the vector genome, suggesting that one or more E4 open reading frames of subgroup C Ad initiate a "pro-life" program that modifies cultured endothelial cells to survive for prolonged periods [19].
• Enforced expression of p14 NF-E4 in the K562 fetal/erythroid cell line, and in primary erythroid cord blood progenitors, results in repression of gamma-gene expression [20].
• This effect is specific, as enforced expression of a mutant form of p14 NF-E4, which fails to interact with CP2, also fails to repress gamma-gene expression in K562 cells [20].

Associations of UBE4A with chemical compounds

• An 8-bp sequence (ATTTCAAA) within the protected region shares significant homology with promoter sequences required for ethylene responsiveness from the tomato fruit-ripening E4 gene [21].
• For instance, the ability of E4 to alter E2F1 function is dependent upon sequences within a putative leucine repeat of E2F1 as well as within the C-terminal acidic domain [22].
• In conclusion, fast cholesterol crystallization is associated with multiple stones but not with apolipoprotein E4 [23].
• A structural model of our E4 peptide/HLA-DQ8 complex predicted that the guanidinyl side chain on the arginine residue at position 6 of the peptide could exist in different orientations [24].
• For this purpose, we have fused the promoter region of the E4 gene to the bacterial gene coding for chloramphenicol acetyl transferase [25].

Other interactions of UBE4A

• 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 [15].

Analytical, diagnostic and therapeutic context of UBE4A

• These observations suggest that E4 is a rate-limiting factor in the degradation of pathological forms of ataxin-3, and that targeted expression of E4B is a potential gene therapy for SCA3 [26].
• T antigen f was seen by immunofluorescence as flecks in these cells, in which the E4 gene was transcribed, but was not seen in E1Y cells, suggesting that T antigen f was encoded by the E4 gene [27].
• Indirect immunofluorescence analyses revealed that more than 99% of the cells that made up the 9ORF1-transfected pools expressed 9ORF1 protein and, together with confocal laser scanning microscopy, indicated that this E4 protein was located predominantly within the cytoplasm of cells [28].
• T antigen f, one of the E4 gene products, was identified as a polypeptide of molecular weight 11,000 (E4- 11K ) by immunoprecipitation with monoclonal antibodies [27].
• In a cross-sectional study, titers of antibodies to the E4 and E7 proteins of human papillomavirus (HPV) type 16 were measured by peptide-based enzyme-linked immunosorbent assay in 1707 sera [29].

References