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

Adenovirus early region 1A (E1A) is the first transcription unit expressed after infection. It encodes a protein which controls the expression of all other early viral genes. The E1A mRNAs have one major capped 5' terminus which maps 31 nucleotides downstream from a T-A-T-A sequence (C. Baker and E. Ziff. J. Mol. Biol. 149:189-221, 1981). In addition, a minor set of E1A mRNAs are observed during the early phase of infection which have 5' termini mapping at approximately -160, -185, and -230 relative to the major cap site (Osborne et al., Cell 29:139-148, 1982). Here we report the occurrence of another set of minor E1A mRNAs which were observed exclusively after the initiation of viral DNA replication. These late specific E1A mRNAs had cap sites which mapped at approximately -300, -325, -360, and -375 relative to the major cap site. The appearance of these minor late E1A mRNAs was blocked by the DNA synthesis inhibitor cytosine arabinoside. These same late specific E1A mRNAs were synthesized from E1A-containing plasmids which replicate in monkey cells. This demonstrated that neither late specific adenovirus proteins nor adenovirus-specific chromatin structure was required for the production of the late specific E1A mRNAs. Adenovirus mutants in which the E1A T-A-T-A box region had been deleted also synthesized the corresponding deleted forms of the late specific mRNAs after initiation of DNA replication. These results indicate that the process of DNA replication alters the specificity of E1A transcription initiation in a promoter region which is at least 375 nucleotides in length.
 ...
PMID:Far upstream initiation sites for adenovirus early region 1A transcription are utilized after the onset of viral DNA replication. 683 69

Viruses are thought to facilitate bacterial infections of the respiratory tract, but the mechanisms are poorly understood. The present study analyzed the effect of adenovirus on bacterial adherence to human respiratory tract epithelial cells. The human lung carcinoma cell line A549 was infected with adenovirus of types 1, 2, 3, 4, 5, and 9. At a multiplicity of infection of 75 particles per cell, cytopathic effects occurred in 75 to 100% of the cells within 48 h. The virus-infected cells were harvested at various times after infection and analyzed for the ability to bind strains of Haemophilus influenzae and Streptococcus pneumoniae. Adenovirus (types 1, 2, 3, and 5) commonly causing respiratory tract infections increased the binding of adherent S. pneumoniae strains to the cells. This effect was not seen for other adenovirus types. Adenovirus infection did not change the adherence of cells of poorly adhering strains of S. pneumoniae or H. influenzae. The increase in adherence of S. pneumoniae could be inhibited by the DNA synthesis inhibitor cytosine arabinofuranoside, which is known to block the late phase of the adenovirus infection. When electron microscopy was used, there was no evidence that virus particles bound directly to bacteria. Adherence was not affected by pretreatment of the cells with virus particles or viral proteins. This suggested that adenovirus infection upregulated receptors for S. pneumoniae. The increased attachment may be one mechanism by which viruses precondition the respiratory mucosa for bacterial infection.
 ...
PMID:Adenovirus infection enhances in vitro adherence of Streptococcus pneumoniae. 800 61

Cellular transformation by the adenovirus E1A oncoprotein requires its p300/CBP- and Rb-binding domains. We mapped inhibition of p53-mediated transactivation to the p300/CBP-binding region of E1A. An E1A mutant incapable of physically interacting with Rb retained the capacity to inhibit transactivation by p53, whereas E1A mutants of the p300/CBP-interacting domain failed to inhibit p53. The inhibitory effect of the p300/CBP-binding region of E1A on p53 was demonstrated with p53-activated reporters and endogenous p53 targets such as p21(WAF1/CIP1) or MDM2. E1A lacking the capacity to interact with Rb, but capable of p300/CBP interaction, was competent in suppression of a DNA-damage activated p53-dependent cell cycle checkpoint. Exogenous CBP and p300 were able to individually relieve E1A's inhibitory effect on p53-mediated transcription. Mutants of E1A that are not capable of interacting with p300 or CBP were found to efficiently stabilize endogenous p53 but were not competent in repression of p21 expression thus dissociating these two effects of E1A. Our results suggest that the p300/CBP-binding domain of E1A inhibits a p53-dependent cellular response which normally inhibits DNA replication following Adenovirus infection.
 ...
PMID:Inhibition of p53-mediated transactivation and cell cycle arrest by E1A through its p300/CBP-interacting region. 907 Jun 53

Cell cycle regulatory proteins are important candidates for therapeutic tumour suppressors. Adenovirus vectors were constructed to overexpress cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 under the control of the murine cytomegalovirus immediate early gene promoter. These vectors directed the efficient expression of each of the cyclin kinase inhibitors and induced growth arrest, inhibited DNA synthesis, and prevented phosphorylation of the retinoblastoma protein (pRb) in cell lines expressing functional pRb. In pRb-deficient cells, expression of the cyclin kinase inhibitors was not effective in inhibiting DNA replication or growth arrest. Interestingly, three of the cyclin kinase inhibitors, p16, p18 and p27 were found to induce apoptotic death in transduced HeLa and A549 cells. When the vectors were tested for their ability to inhibit tumorigenicity in a polyomavirus middle T antigen model of murine breast carcinoma, expression of the cyclin kinase inhibitors resulted in a delay in tumour formation that varied from several weeks for the p19 expressing vector to greater than 25 weeks for the p27 expressing vector. When tumours were injected directly with the adenovirus vectors expressing the cyclin kinase inhibitors, only treatment with the vector expressing p16 resulted in a delay in tumour growth.
 ...
PMID:Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity. 1020 28

In axotomized adult neurons, a process of axonal regrowth and re-establishment of the neuronal function has to be activated. Developmentally regulated factors may be reactivated during neuronal regeneration. Here we identify a gene, previously designated P311, that is up-regulated in the axotomized facial motoneurons. Ectopically expressed P311 localizes in the cytoplasm and the nucleus. Over-expression of P311 induces p21(WAF1/Cip1) expression, leading PC12 cells to differentiate and to have neuron-like morphologies. Adenovirus-mediated P311 gene transfer promotes neurite outgrowth of postnatal dorsal root ganglion neurons and embryonic hippocampal neurons in vitro. This effect is abolished by the activation of Rho kinase. P311 also facilitates nerve regeneration following facial nerve injury in vivo. Our data provide evidence that genes involved in the differentiation process contribute to the regeneration of injured mature neurons, and may provide a practical molecular target.
 ...
PMID:P311 accelerates nerve regeneration of the axotomized facial nerve. 1548 2

Adenovirus E1A-associated p400 belongs to the SWI2/SNF2 family of chromatin remodeling proteins. Here, we report that p400 is a component of the p53-p21(WAF1/CIP1/sid1) pathway, regulating the p21 transcription and senescence induction program. Acute depletion of p400 expression by shRNA (short hairpin RNA) synthesis led to premature senescence of untransformed human fibroblasts, whose features include G1 arrest, p21 induction, senescence-associated heterochromatic foci (SAHF), and beta-gal staining. Importantly, p400shRNA-induced premature senescence phenotypes were rescued by coexpression of p53-shRNA or p21-shRNA. Furthermore, p400 complex colocalized with p53 on the p21 promoter. These data suggest that the p400 complex inhibits p53 --> p21 transcription and the development of premature senescence.
 ...
PMID:The p400 E1A-associated protein is a novel component of the p53 --> p21 senescence pathway. 1565 9

Oxidative stress-induced cell death plays a major role in the progression of ischemic acute renal failure. Using microarrays, we sought to identify a stress-induced gene that may be a therapeutic candidate. Human proximal tubule (HK2) cells were treated with hydrogen peroxide (H2O2) and RNA was applied to an Affymetrix gene chip. Five genes were markedly induced in a parallel time-dependent manner by cluster analysis, including activating transcription factor 3 (ATF3), p21(WAF1/CiP1) (p21), CHOP/GADD153, dual-specificity protein phosphatase, and heme oxygenase-1. H2O2 rapidly induced ATF3 approximately 12-fold in HK2 cells and approximately 6.5-fold in a mouse model of renal ischemia-reperfusion injury. Adenovirus-mediated expression of ATF3 protected HK2 cells against H2O2-induced cell death, and this was associated with a decrease of p53 mRNA and an increase of p21 mRNA. Moreover, when ATF3 was overexpressed in mice via adenovirus-mediated gene transfer, ischemia-reperfusion injury was reduced. In conclusion, ATF3 plays a protective role in renal ischemia-reperfusion injury and the mechanism of the protection may involve suppression of p53 and induction of p21.
 ...
PMID:ATF3 protects against renal ischemia-reperfusion injury. 1823 2

EBV-associated nasopharyngeal cancer (NPC) occurs with high frequency in China and is a major cause of morbidity and mortality. To explore the potential use of adenovirus-mediated tumor suppressor p53 gene therapy In NPC, we first examined the in vitro effects of p53 introduced into the NPC cell lines RPMI 2650, Fadu and Detroit 562. p21(WAF1/CIP1) induction by chemotherapy was used as a functional assay which revealed that RPMI 2650 expresses wild-type p53 whereas Fadu and Detroit 562 encode mutant p53. Infection with p53-expressing adenovirus (Ad-p53) induced apoptosis and inhibited cell growth in all three NPC cell lines, regardless of the endogenous p53 status. Adenovirus infectivity was greatest in RPMI 2650 cells, with 100% of the cells expressing beta-galactosidase following Ad-LacZ infection using an MOI of 100, as compared to 20-30% infectivity with the other NPC lines. Using RPMI 2650 cells injected into nude mice, we developed an animal model for nasopharyngeal cancer. Established tumors (0.6-0.8 cm) were injected with 5x10(9) PFU Ad-LacZ, Ad-p53 or PBS in a 100 mu l volume. We found evidence for in vivo expression of beta-galactosidase or p53 and p21 up to two weeks following Ad-LacZ or Ad-p53 virus injection respectively. Objective regression of tumor size was observed at two weeks in 4/6 Ad-p53-treated tumors, but not in Ad-LacZ or PBS-treated tumors. The results provide an animal model for human nasopharyngeal cancer, and indicate a potential use of p53 in its therapy in vivo.
 ...
PMID:Adenovirus-mediated p53 gene therapy in nasopharyngeal cancer. 2152 3