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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An in vitro transcription system has been developed from 0.3M NaCl extracts of nuclei of Drosophila embryos. Optimal transcription in the Drosophila embryo extract (DEX) was at 5mM MgCl2, 70mM KCl, 25 degrees C and with promoter concentrations of 0,75-1.0 pmol/assay. In vitro transcription from the Adenovirus-2 major late and the Drosophila histone gene promoters was studied in particular. S1-nuclease protection experiments showed that in vitro transcription from these promoters was accurate. In vitro transcription from the Adenovirus-2 major late promoter was less efficient than from histone gene H3 and H4 promoters in DEX. Vicecersa, in vitro transcription from Adenovirus-2 major late promoter was more efficient in HeLa whole cell extracts. The efficiencies of transcription from histone gene promoters decreased in DEX in the order H4 greater than or equal to H3 greater than H2a. Transcription from H2b and H1 promoters was not detected in DEX. The transcription from the Adenovirus-2 major late promoter was completely inhibited by histone H3 and H4 promoters. Preincubation of DEX with the adenoviral template, however, did not inhibit transcription from histone H3 and H4 promoters. The transcription start sites of histone genes H3 and H4 are separated by 160 base pairs. The H3 and H4 transcription start sites were subcloned separately. Now, a competition of transcription from the H3/H4 promoters with the Adenovirus-2 major late promoter was observed. The competition studies suggest that preincubation of DEX with the adenoviral template inhibited transcription from the H3 promoter more strongly than from the H4 promoter.
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PMID:In vitro transcription with extracts of nuclei of Drosophila embryos. 298 64

Adenovirus chromatin is constituted with three kinds of core proteins, VII, V, and mu, that are coded by the virus genome. Since a hexamer of VII contributes to formation of the nucleosome-like structure of the virion chromatin, we analyzed the interaction between DNA and VII in vitro, by the use of ultraviolet light-induced cross-linking and circular dichroism (CD) spectroscopy. It was observed that DNA and VII in a plain mixture form a structure resembling viral chromatin. The DNA in the virion core or in the simply mixed complex appears to take a tight conformation by superfolding, based on the result that the ellipticity at 275 nm of DNA was reduced to approximately 3,000 degrees, and the wave-length of the positive peak was shifted from 275 to 285 nm. The change in CD spectrum caused by interaction of VII with DNA is similar to that of a protamine rather than that of a histone mixture. The interaction of VII with DNA is preferential, and VII is capable of associating more efficiently with double stranded DNA than with single stranded. The interaction is loosened by salt (0.3 M NaCl) and tightened by magnesium ion. However, the interaction of a precursor core protein pro-VII with DNA was not as tight as that of VII and was not influenced by magnesium ion, presumably because of the existence of a hydrophobic processing sequence in the molecule.
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PMID:Analysis of the interaction between DNA and major core protein in adenovirus chromatin by circular dichroism and ultraviolet light induced cross-linking. 674 86

We examined acetylation of the histone-like adenovirus core proteins VII and V and the precursor of the major core protein, pVII, by measuring the incorporation of [14C]acetate. Adenovirus proteins pVII and V appeared to be acetylated, whereas protein VII was not. Label incorporated into these viral proteins in the form of acetate was metabolically stable, and labeling was not enhanced by treatment with sodium butyrate, an inhibitor of histone deacetylases. Viral protein acetylation therefore differs from the reversible acetylation of histones that has been implicated in transient alterations of chromatin structure. Inhibition of protein synthesis in infected cells resulted in a proportional reduction in [14C]acetate uptake into pVII and V, suggesting that these proteins undergo acetylation during protein synthesis and not as a post-translational modification. Therefore, these viral proteins are probably acetylated amino-terminally, a characteristic shared by three of the five major histone classes.
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PMID:Acetylation of histone-like proteins of adenovirus type 5. 742 May 37

Adenovirus E1A mediates its effects on cellular transformation and transcription by interacting with critical cellular proteins involved in cell growth and differentiation. The amino terminus of E1A binds to CBP/p300 and associated histone acetyltransferases such as P/CAF. The carboxyl terminus binds to the carboxyl-terminal binding protein (CtBP), which associates with histone deacetylases. We show that 12S E1A can be acetylated by p300 and P/CAF and map one of the acetylation sites to Lys-239. This Lys residue is adjacent to the consensus CtBP binding motif, PXDLS. Mutation of Lys-239 to Gln or Ala blocks CtBP binding in vitro and disrupts the E1A-CtBP interaction in vivo. Peptide competition assays demonstrated that the interaction of E1A with CtBP is also blocked by Lys-239 acetylation. Supporting a functional role for Lys-239 in CtBP binding, mutation of this residue to Ala decreases the ability of E1A to block cAMP-regulated enhancer (CRE)-binding protein (CREB)-stimulated gene expression. Finally, we demonstrate that Lys-239 is acetylated in cells by using an antibody directed against an acetyl-Lys-239 E1A peptide. CtBP interacts with a wide variety of other transcriptional repressors through the PXDLS motif, and, in many instances, this motif is followed by a Lys residue. We suggest that acetylation of this residue by histone acetyltransferases, and the consequent disruption of repressor complexes, might be a general mechanism for gene activation.
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PMID:Acetylation of adenovirus E1A regulates binding of the transcriptional corepressor CtBP. 1111 58

The aim of this work was to identify proteins from Adenovirus 2-infected HeLa cell extracts that interact with the carboxyl-terminal domain of the largest subunit of RNA polymerase II. First, a mammalian RNA polymerase II complex was isolated from Adenovirus 2-infected HeLa cell extracts by affinity chromatography against the carboxyl-terminal domain of the largest subunit of RNA polymerase II, followed by chromatography on a Mono S fast protein liquid chromatographic column. Second, the isolated complex was further characterized by Western blot analysis, the formation of a GMP-protein complex, and transcriptional activity. The isolated complex contains general transcription factors, chromatin-remodeling factors, histone acetyltransferases, Srbs, capping enzymes, and E1A viral oncoproteins. The RNA polymerase II complex is active in transcription when supplemented with recombinant transcription factor IIB.
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PMID:An RNA polymerase II complex containing capping enzymes and viral oncoproteins. 1118 57

The cAMP-response element-binding protein (CREB)-binding protein and p300 are two highly conserved transcriptional coactivators and histone acetyltransferases that integrate signals from diverse signal transduction pathways in the nucleus and also link chromatin remodeling with transcription. In this report, we have examined the role of p300 in the control of the G(1) phase of the cell cycle in nontransformed immortalized human breast epithelial cells (MCF10A) and fibroblasts (MSU) by using adenovirus vectors expressing p300-specific antisense sequences. Quiescent MCF10A and MSU cells expressing p300-specific antisense sequences synthesized p300 at much reduced levels and exited G(1) phase without serum stimulation. These cells also showed an increase in cyclin A and cyclin A- and E-associated kinase activities characteristic of S phase induction. Further analysis of the p300-depleted quiescent MCF10A cells revealed a 5-fold induction of c-MYC and a 2-fold induction of c-JUN. A direct target of c-MYC, CAD, which is required for DNA synthesis, was also found to be up-regulated, indicating that up-regulation of c-MYC functionally contributed to DNA synthesis. Furthermore, S phase induction in p300-depleted cells was reversed when antisense c-MYC was expressed in these cells, indicating that up-regulation of c-MYC may directly contribute to S phase induction. Adenovirus E1A also induced DNA synthesis and increased the levels of c-MYC and c-JUN in serum-starved MCF10A cells in a p300-dependent manner. Our results suggest an important role of p300 in cell cycle regulation at G(1) and raise the possibility that p300 may negatively regulate early response genes, including c-MYC and c-JUN, thereby preventing DNA synthesis in quiescent cells.
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PMID:Antisense-mediated depletion of p300 in human cells leads to premature G1 exit and up-regulation of c-MYC. 1129 95

Adenovirus infection of quiescent cells induces transition from G0 or G1 into the S phase of the cell cycle and allows cellular proliferation. This is beneficial for the virus since cells in S phase provide optimal conditions for viral replication. Adenovirus E1A, E1B and E4 gene products contribute to cell cycle deregulation. E1A proteins inactivate the pRb checkpoint, allowing the E2F transcription factor to activate genes involved in nucleotide metabolism and DNA replication, which are required in S phase. E1A also interacts with transcriptional modulators, including histone acetyltransferases, histone deacetylases, and other chromatin remodeling factors. These interactions affect transcription of several cellular and viral genes, some of which are involved in cell cycle regulation. Cell cycle deregulation by E1A results in stabilization and accumulation of p53. To prevent cell cycle arrest and apoptosis that would be triggered by p53, the adenovirus E1B and E4orf6 gene products employ various mechanisms to inactivate the tumor suppressor. Additional E4 gene products also interact with and modulate cell cycle regulators. Cell cycle checkpoints targeted by adenovirus proteins are often compromised in human tumors as well. Thus, understanding the interactions between adenovirus and the cell cycle has facilitated the generation of adenovirus mutants, which can replicate only in cells with inactivated checkpoints. Such "oncolytic" viruses are being tested for their ability to specifically replicate in and lyse cancer cells.
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PMID:Adenovirus and cell cycle control. 1199 31

Toll-like receptor-4 (TLR4) and its signaling molecule interleukin-1 receptor-associated kinase (IRAK-1) play an important role in host defense and tissue inflammation. Intriguingly, systemic administration of lipopolysaccharide (LPS), the agonist for TLR4, confers a cardio-protective effect against ischemic injury. However, the mechanisms leading to the cardiac protection remain largely unknown. The present study was designed to investigate the role of TLR4 activation by LPS in protecting cardiomyocytes (CM) against apoptosis in an in vitro model of ischemia and to explore the downstream mechanisms leading to the protective effect. Incubation with LPS led to activation of IRAK-1 and protected CMs against serum deprivation (SD)-induced apoptosis as demonstrated by DNA laddering, histone-DNA fragment enzyme-linked immunosorbent assay, and activation of caspase-3. Phosphatidylinositol 3-kinase/Akt, extracellular signal-regulated kinase 1/2, and IkappaB kinase beta appear to contribute to the anti-apoptotic effect of LPS since the specific inhibitors, wortmannin, PD98059, and dominant negative IKKbeta transgene expression reversed the LPS effect. To assess whether LPS improves CM function, we examined intracellular Ca(2+) transients and cell shortening in single adult rat CMs. SD for 6 h dramatically inhibited Ca(2+) transients and CM contractility. LPS at 500 ng/ml significantly improved the [Ca(2+)](i) transients and enhanced contractility in control CMs as well as in CMs subjected to SD. Importantly, transient ischemia led to rapid activation of IRAK-1 in cultured CMs and in adult rat myocardium. Adenovirus-mediated transgene expression of IRAK-1 but not its kinase-deficient mutant IRAK-1(K239S) protected CMs against SD-induced apoptosis. Taken together, these data suggest an important role of TLR4 signaling via IRAK-1 in protecting against SD-induced apoptosis.
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PMID:Lipopolysaccharide improves cardiomyocyte survival and function after serum deprivation. 1579 10

Adenovirus small early region 1a (e1a) protein drives cells into S phase by binding RB family proteins and the closely related histone acetyl transferases p300 and CBP. The interaction with RB proteins displaces them from DNA-bound E2F transcription factors, reversing their repression of cell cycle genes. However, it has been unclear how the e1a interaction with p300 and CBP promotes passage through the cell cycle. We show that this interaction causes a threefold reduction in total cellular histone H3 lysine 18 acetylation (H3K18ac). CBP and p300 are required for acetylation at this site because their knockdown causes specific hypoacetylation at H3K18. SV40 T antigen also induces H3K18 hypoacetylation. Because global hypoacetylation at this site is observed in prostate carcinomas with poor prognosis, this suggests that processes resulting in global H3K18 hypoacetylation may be linked to oncogenic transformation.
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PMID:Adenovirus small e1a alters global patterns of histone modification. 1871 83

Adenovirus e1a induces quiescent human cells to replicate. We found that e1a causes global relocalization of the RB (retinoblastoma) proteins (RB, p130, and p107) and p300/CBP histone acetyltransferases on promoters, the effect of which is to restrict the acetylation of histone 3 lysine-18 (H3K18ac) to a limited set of genes, thereby stimulating cell cycling and inhibiting antiviral responses and cellular differentiation. Soon after expression, e1a binds transiently to promoters of cell cycle and growth genes, causing enrichment of p300/CBP, PCAF (p300/CBP-associated factor), and H3K18ac; depletion of RB proteins; and transcriptional activation. e1a also associates transiently with promoters of antiviral genes, causing enrichment for RB, p130, and H4K16ac; increased nucleosome density; and transcriptional repression. At later times, e1a and p107 bind mainly to promoters of development and differentiation genes, repressing transcription. The temporal order of e1a binding requires its interactions with p300/CBP and RB proteins. Our data uncover a defined epigenetic reprogramming leading to cellular transformation.
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PMID:Epigenetic reprogramming by adenovirus e1a. 1871 84


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