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

Numerous clinical, epidemiological and molecular findings link some types of Human Papillomaviruses (HPV) with cancer of the genital tract. They share a common pathway of transformation with a number of DNA tumour viruses, such as Adenovirus and SV40. Although all these viruses are termed 'DNA tumour viruses' and have similar in vitro transforming activities, Human Papillomavirus is the only one so far clearly involved in human cancer. Extensive studies on HPV E6 and E7 proteins have demonstrated their involvement in malignant transformation. E6 and E7 bind the products of tumour suppressor genes, p53 and Rb1, respectively, modifying or inactivating their normal functions. The Rb1 and p53 genes are deleted or mutated in several cancers and both proteins regulate the transcription of genes involved in cell cycle progression control. The E6/p53 and E7/Rb1 interactions result in a deregulation of the cell cycle with loss of control of crucial cellular events, such as DNA replication, DNA repair and apoptosis.
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PMID:Human papillomavirus E6 and E7: proteins which deregulate the cell cycle. 757 92

Hygromycin B, an aminoglycoside antibiotic that is widely used to establish stable mammalian cell lines that carry a bacterial gene conferring resistance to the drug, is shown here to induce apoptotic programmed cell death in susceptible cells. Dying cells exhibited typical features of apoptosis, including cell shrinkage, membrane blebbing, nuclear pyknosis, and extensive internucleosomal fragmentation of DNA. Employing concentrations of hygromycin B that are typically used for selecting stable cell lines, we show that susceptible cells die rapidly, exhibiting the morphological properties of apoptosis by 18 h and detectable DNA fragmentation as early as 2 h after receiving the drug. G418, on the other hand, required days to cause cell death, which was not accompanied by internucleosomal DNA fragmentation. Apoptotic cell killing by hygromycin B did not require expression of wild-type p53 and was suppressed by both Bcl-2 and the Adenovirus type 5 E1B 19-kDa protein.
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PMID:Induction of p53-independent apoptosis by hygromycin B: suppression by Bcl-2 and adenovirus E1B 19-kDa protein. 758 55

Adenovirus E1B 19K protein prevents premature death of adenovirus-infected cells. Viral mutants (19K mutants) defective in the 19K protein induce enhanced cell death, resulting in fragmentation of viral and cellular DNA. The 19K protein can also suppress the effects of certain external cell death-inducing stimuli, such as tumor necrosis factor alpha and various DNA-damaging agents that induce apoptosis. We have examined viral infection of permissive human cells and nonpermissive rat cells to determine if the 19K mutant induces apoptotic or necrotic type of cell death. Infection of normal rat kidney cells with an adenovirus type 2 19K deletion mutant induces internucleosomal DNA fragmentation and condensation of nuclear chromatin. Electron microscopic examination of these cells revealed the presence of condensed subnuclear bodies characteristic of apoptosis. In contrast, infection of human A549 cells induces random DNA fragmentation, and these cells do not exhibit characteristic condensation of the nuclear chromatin but contain enlarged nuclei loaded with virus particles. Therefore, it appears that adenovirus infection induces both apoptotic and necrotic types of cell death, depending on the cell type. Both types of cell death can be suppressed by E1B 19K protein. Similarly, a recombinant adenovirus expressing the human Bcl-2 protein but lacking the E1B proteins can efficiently suppress both apoptotic and necrotic cell death induced by adenovirus infection. The requirement of p53 tumor suppressor protein in adenovirus-induced cell death was investigated by infection of human Saos2 and mouse p53 nullizygous (p53-/-) cells lacking p53 tumor suppressor protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:p53-independent apoptotic and necrotic cell deaths induced by adenovirus infection: suppression by E1B 19K and Bcl-2 proteins. 775 71

Adenovirus E1A expression recruits primary rodent cells into proliferation but fails to transform them because of the induction of programmed cell death (apoptosis). The adenovirus E1B 19,000-molecular-weight protein (19K protein), the E1B 55K protein, and the human Bcl-2 protein each cause high-frequency transformation when coexpressed with E1A by inhibiting apoptosis. Thus, transformation of primary rodent cells by E1A requires deregulation of cell growth to be coupled to suppression of apoptosis. The product of the p53 tumor suppressor gene induces apoptosis in transformed cells and is required for induction of apoptosis by E1A. The ability of Bcl-2 to suppress apoptosis induced by E1A suggested that Bcl-2 may function by inhibition of p53. Rodent cells transformed with E1A plus the p53(Val-135) temperature-sensitive mutant are transformed at the restrictive temperature and undergo rapid and complete apoptosis at the permissive temperature when p53 adopts the wild-type conformation. Human Bcl-2 expression completely prevented p53-mediated apoptosis at the permissive temperature and caused cells to remain in a predominantly growth-arrested state. Growth arrest was leaky, occurred at multiple points in the cell cycle, and was reversible. Bcl-2 did not affect the ability of p53 to localize to the nucleus, nor were the levels of the p53 protein altered. Thus, Bcl-2 diverts the activity of p53 from induction of apoptosis to induction of growth arrest, and it is thereby identified as a modifier of p53 function. The ability of Bcl-2 to bypass induction of apoptosis by p53 may contribute to its oncogenic and antiapoptotic activity.
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PMID:Bcl-2 blocks p53-dependent apoptosis. 813 58

Adenovirus-(Ad)- E1A proteins carry two conserved domains (CR1 and CR2) required for transformation of primary rodent cells and essential for association with cellular proteins, including p105RB, p58cyclin A and p33cdk2. We show that in normal rat kidney 49F (NRK) cell lines expressing various mutant Ad5-E1A genes, CR2-, but not CR-1-, deletion mutants induce a typical transformed phenotype as characterized by morphology, absence of density arrest and loss of serum requirement. This indicates that induction of these transformed properties is a function of CR1. The fact that E1A proteins with deletions in CR2 show a greatly reduced association with RB, cyclin A and p33cdk2 suggests that these associations are dispensable for E1A-mediated transformation of NRK cells. Induction of the transformed properties is accompanied by a CR1-dependent increase in Proliferating Cell Nuclear Antigen and cyclin A gene expression. Elevated mRNA and protein levels of cyclin A were also found in Ad12-E1-transformed NRK cells but not in ras-transformed NRK cells. On the other hand, cyclin D expression is decreased in a CR1-dependent manner. Although Ad5-E1A proteins are sufficient to transform NRK cells, further deregulation of growth is obtained when Ad5-E1B proteins are co-expressed. One of the Ad5-E1B effects is the sequestration of the p53 protein into a cytoplasmic body containing the p53/Ad5-E1B-55 kD complex. Interestingly, in NRK cell lines expressing Ad5-E1B-55 kD, cyclin A could be detected not only in the nucleus but also in the cytoplasmic bodies. These results indicate that the deregulation of cell cycle control by the Adenovirus-E1 region may be due to a CR1-dependent alteration of the expression of cyclins A and D.
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PMID:Increased cyclin A and decreased cyclin D levels in adenovirus 5 E1A-transformed rodent cell lines. 851 Sep 23

Homeostasis of cell numbers in tissues is maintained by a critical balance between cell proliferation and programmed cell death or apoptosis. Many human viruses are able to develop suitable strategies for modifying apoptosis in virus-infected cells and in virus-primed T cells. Apoptosis is characterized by the fragmentation of nuclear DNA into 180-200 bp apoptotic bodies and can be analysed microscopically or by flow cytometry using staining with various dyes. Moreover DNA cleavage can be identified by electrophoresis and by specific labeling using in situ nucleotidyltransferase assay (ISNT), terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling technique (Tunel), or by Elisa. Adenovirus E1A induces expression of protooncogenes c-myc and c-fos which sensitize cells to apoptosis; EBV EBNA-5, and adenovirus E1A, HPV E7, and polyomavirus large T act in the same way by displacing pRB-bound E2F. EBV EBNA-5, HPV E6, Adenovirus E1B 55 kDa inactivate the tumor suppressor protein p53 and engage the cells in the transformation process. EBV LMP-1, HHV6, and HTLV1 tax induce the antiapoptotic bcl-2 protein. EBV BHRF1 encodes proteins with homology to bcl-2 and Adenovirus E1B 19 kDa encodes proteins that have protective functions similar to bcl-2. Activated lymphocytes responding to viral infections express high levels of fas and are susceptible to apoptosis. TNF alpha can down- or up-regulate fas and down-regulates TNF-R. Adenovirus E1B 19 kDa blocks the proapoptotic activity of TNF alpha. Inversly, Cytomegalovirus, hepatitis C virus and Myxoviruses up-regulate fas antigen prior to undergoing apoptosis. In HIV-infected patients, CD4+ T-cell apoptosis is mediated by the cytopathic effect of the virus and the cell surface expression of gp 120-env protein. Moreover, an accelerated T-cell apoptosis in HIV-infected individuals is characterized by (i) HIV gp120-CD4+ cross-linking and subsequent aberrant signaling of T-cells, (ii) involvement of TNF alpha-fas/Apo-1 (TNF-R) binding, (iii) involvement of accessory cells as an apoptosis inducer and as a result of defective antigen presentation, (iv) possible superantigen activity induced by HIV products and cofactors. Many viruses also encode proteins with protease activity which could induce apoptosis. The induction of apoptosis may result in virus clearance, in contrast the inhibition of apoptosis may result in virus cell transformation and viral persistence. Indirectly, the apoptosis of infected cells may be induced by CTLs, NK cells and cytokines. In addition, apoptosis-mediated physiological depletion of T lymphocytes in the course of viral infection can silence the immune response and can induce immunodeficiency.
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PMID:[Apoptosis and human viral infections]. 886 58

We have previously reported on radiation-induction of ptk-3 in rat astrocyte culture [Sakuma et al. (1995) Radiat. Res. 143, 1-7]. Ptk-3 was considered to be a rat version of human DDR (discoidin domain receptor). We cloned and analyzed genomic DNA of the DDR and its promoter region. We discovered that the promoter region contained a consensus sequence of the p53 tumor suppressor binding site. Adenovirus-mediated p53 transfection induced a high level of DDR mRNA in SAOS2 human osteosarcoma cells. These results indicate that DDR is up-regulated by the p53 protein.
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PMID:Receptor protein tyrosine kinase DDR is up-regulated by p53 protein. 897 99

The major transforming protein of human papillomaviruses (HPVs) is encoded by the E7 gene. This protein cooperates with activated oncogenes to transform primary rodent cells and with the viral E6 gene to immortalize primary human keratinocytes. Numerous cellular targets of HPV E7 have now been identified including pRb, p107, cyclin A, TATA box binding protein (TBP), and members of the AP-1 transcription factor family. As with Adenovirus E1a, many of these interactions are important for the ability of E7 to transform cells. Recent studies have demonstrated that Adenovirus E1a can also inhibit the transcriptional activity of the cellular tumor suppressor protein, p53. We have performed a series of analyses to determine whether HPV E7 proteins share this characteristic. We show that HPV E7 proteins derived from both benign and tumor-associated HPV types are able to inhibit p53 transcriptional activity. Mutational analysis of the HPV-16 E7 protein reveals that a key domain involved in mediating this activity is the casein kinase II (CKII) recognition site, which has been shown to modulate E7 binding to TBP. We further show that E7 does not bind to p53 directly, but will do so in the presence of exogenously added TBP and that this binding is increased following CKII phosphorylation. These results suggest that the E7-TBP interaction may be responsible for inhibiting p53 transcriptional activity.
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PMID:Repression of p53 transcriptional activity by the HPV E7 proteins. 900 83

Overexpression of the tumour suppressor gene product p53 is common in oesophageal adenocarcinoma. This may be due to gene mutation, but overexpression can also result from complexing between viral proteins and p53; a number of viruses are causally linked with malignancy. This study therefore investigated the prevalence in oesophageal adenocarcinoma of viruses whose gene products are capable of interacting with p53. Seventeen tumours and 17 normal oesophagi were screened for specific DNA sequences from human papilloma virus (HPV), Adenovirus type 12, Epstein-Barr Virus (EBV), and cytomegalovirus (CMV). Frozen sections were analysed by polymerase chain reaction, and results were confirmed by Southern blot hybridization. Overexpression of p53 was studied immunohistochemically. Overexpression of p53 was identified in 11 of 17 tumours. No viral sequences were detected for HPV, CMV, or Adenovirus in any tumour. EBV sequences were found in eight of 17 tumours, and eight of 17 negative controls. There is therefore no evidence of HPV 16, 18 and 33, Adenovirus 12 or CMV infection in oesophageal adenocarcinoma. EBV infection in the oesophagus is of doubtful significance, in view of the high incidence in the control population. Overexpression of p53 cannot be explained by complexing with common viral proteins, and must be related to other intracellular mechanisms.
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PMID:Investigation of oesophageal adenocarcinoma for viral genomic sequences. 906 43

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.
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PMID:Inhibition of p53-mediated transactivation and cell cycle arrest by E1A through its p300/CBP-interacting region. 907 Jun 53


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