Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated a rat cDNA, named FE65, hybridizing to an mRNA of about 2,300 nucleotides present in rat brain, undetectable in rat liver and very poorly represented in other tissues. An mRNA of the same size is present in human neuroblastoma cells and is absent from other human cell lines. The FE65 cDNA contains an open reading frame (ORF) coding for a polypeptide of 499 amino acids in which 143 residues can be aligned with the DNA binding domain of the integrases encoded by mammalian immunodeficiency viruses. The remaining part of the FE65 ORF is not homologous with the correspondent regions of the integrases; the first 206 residues of the FE65 ORF show numerous negative charges and a short sequence not dispensable for the function of the transactivating acidic domain of the jun family transcriptional factors. A plasmid which expresses FE65 amino acids 1-232 fused to the yeast GAL4 DNA binding domain was co-transfected with a plasmid containing five GAL4 binding sites upstream of a minimal Adenovirus promoter controlling the expression of the CAT gene. This experiment showed that the fused protein GAL4-FE65 is able to obtain a 30-40 fold increase of the CAT gene expression compared to the expression observed in the presence of the GAL4 DNA binding domain alone. Two types of FE65 mRNA are present in rat brain, differing only for six nucleotides. We demonstrate that this is the consequence of a neuron-specific alternative splicing of a six-nucleotide miniexon, which is also present in the human genome, in an intron/exon context very similar to that of the rat FE65 gene.
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PMID:A rat brain mRNA encoding a transcriptional activator homologous to the DNA binding domain of retroviral integrases. 192 10

Adenovirus E1A dependent trans-activation of transcription involves the utilization of cellular promoter specific transcription factors. One such factor termed E2F is important for the transcription of the viral E2 gene and appears to be a rate limiting component targeted during the trans-activation event. Since E2F is of cellular origin and likely to be involved in cellular gene control, we have identified E2F binding sites in cellular genes. Examples include the c-myc, c-myb and N-myc protoncogenes, the DHFR gene and the EGF receptor gene. The transcription of these genes is regulated by cell proliferation signals and each falls into the so-called immediate early class: genes that are activated independent of new protein synthesis. Because of these common properties of regulation, we have addressed the possible role of E2F in growth factor dependent activation of transcription. Expression of a c-myc promoter driven CAT gene, transfected into quiescent 3T3 cells, is stimulated by serum addition whereas an identical gene containing mutations in the E2F binding sites is not responsive. The DNA binding activity of E2F is increased 4-fold upon serum stimulation and the kinetics of activation parallel activation of c-myc transcription. Furthermore, this increase in E2F activity is independent of new protein synthesis indicating that serum stimulation results in an activation of a pre-existing factor. These results thus provide strong evidence linking E2F and proliferation dependent control of transcription. We also believe that the E2F transcription factor is the first example of a regulator of the class of immediate early genes that is slowly activated by stimulation of cell proliferation.
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PMID:A role for the adenovirus inducible E2F transcription factor in a proliferation dependent signal transduction pathway. 214 65

Adenovirus-mediated gene transfer experiments have demonstrated an exceptional efficiency of virus uptake and gene expression in a variety of in vivo models. Unfortunately, the efficiency of gene delivery is not accompanied by long-term gene expression. Maximal gene expression peaks during the first week of infection followed by a rapid decline to near baseline levels within several weeks. Data from several laboratories implicate host cellular and humoral immune responses as being responsible for the limited duration of expression and for the inability to successfully readminister a gene using adenovirus vectors. In this study we have examined two strategies which, independently or in combination, circumvent aspects of the host immune response against adenovirus-mediated gene therapy. The first strategy explores induction of immune tolerance in the experimental host as a method to increase the duration of gene expression and as a method to allow readministration of adenovirus expression vectors. Our second strategy is directed at the need to readminister adenoviral vectors to immune competent adult animals. We have demonstrated that a sequential exposure of rats to at least two other adenovirus serotypes does not compromise our ability to successfully administer an Ad5-based CAT expression vector. The characterization of serotype-specific neutralizing response indicates that the construction and use of Ad expression vectors from different serotypes will facilitate a useful adenovirus-based strategy allowing multiple administrations of a target gene.
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PMID:Circumventing the immune response to adenovirus-mediated gene therapy. 886 63

The basic helix-loop-helix (bHLH) transcription factor myogenin plays a crucial role in terminal differentiation of committed myoblasts into mature myocytes. Transcriptional activation of the myogenin gene requires coordinate action of myocyte enhancer factor 2 (MEF2) proteins and the myogenic bHLH regulators, MyoD or Myf5. Here we show that transcription of the myogenin gene in differentiated cells correlates with MEF2 and NF1 binding to their cognate sites in the proximal myogenin promoter but not with binding of Myf5 or MyoD to the E-box. The importance of MEF2 activity was further demonstrated by expression of antisense MEF2 RNA which repressed MEF2 and Myf5-mediated MEF2 site-dependent reporter gene activation and the synergistic transactivation of a myogenin CAT reporter by Myf5 and MEF2. Adenovirus E1A which has previously been shown to specifically interfere with myogenin gene transcription also inhibited the cooperative transactivation by Myf5/MEF2 and MEF2. Consistently, coimmunoprecipitation studies revealed impaired MEF2/Myf5 protein-protein interactions. These results support a model of transcriptional activation and stabilization of myogenin expression in which DNA-bound MEF2 recruits myogenic bHLH factors into an active but E1A-sensitive transcription factor complex.
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PMID:Transcriptional activation of the myogenin gene by MEF2-mediated recruitment of myf5 is inhibited by adenovirus E1A protein. 1054 18

The SNF2-related CBP activator protein (SrCap) is a potent activator of transcription mediated by CBP and CREB. We have previously demonstrated that the Adenovirus 2 DNA Binding Protein (DBP) binds to SrCap and inhibits the transcription mediated by the carboxyl-terminal region of SrCap (amino acids 1275-2971). We report here that DBP inhibits the ability of full-length SrCap (1-2971) to activate transcription mediated by Gal-CREB and Gal-CBP. In addition, DBP also inhibits the ability of SrCap to enhance Protein Kinase A (PKA) activated transcription of the enkaphalin promoter. DBP was found to dramatically inhibit transcription of a mammalian two-hybrid system that was dependent on the interaction of SrCap and CBP binding domains. We also found that DBP has no effect on transcription mediated by a transcriptional activator that is not related to SrCap, indicating that our reported transcriptional inhibition is specific for SrCap and not due to nonspecific effects of DBP's DNA binding activity on the CAT reporter plasmid. Taken together, these results suggest a model in which DBP inhibits cellular transcription mediated by the interaction between SrCap and CBP.
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PMID:Adenovirus DNA binding protein inhibits SrCap-activated CBP and CREB-mediated transcription. 1295 26