Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis is an active mechanism of cell death which can be initiated in response to various stimuli including virus infections. In this work, we demonstrate that lytic infection by varicella-zoster virus (VZV), a human herpesvirus, is characterized by nuclear fragmentation of DNA into oligonucleosomal fragments and by chromatin condensation. In vitro, VZV-induced cell death is actually mediated by apoptosis. The mechanisms developed by cells to protect themselves against apoptosis could be one of the parameters allowing the establishment of virus latency. In the case of VZV, which can remain latent in sensory ganglia, we have not yet identified a cellular or viral protein which could play this protective role, since the observed apoptosis mechanism seems to be independent from Bcl-2, the most frequently described inhibitor of apoptosis.
J Gen Virol 1995 Nov
PMID:Varicella-zoster virus induces apoptosis in cell culture. 759 98

In this study, the immunohistochemical expression of bcl-2 protein in benign and malignant lymphoid aggregates in bone marrow biopsies was investigated in order to estimate its significance in distinguishing the biologic nature of the aggregates. Paraffin-embedded tissues of 46 bone marrow biopsies were stained with a monoclonal antibody to bcl-2 protein using the supersensitive streptavidin biotin immunoperoxidase method after a microwave heating of the sections. Bcl-2 protein immunoreactivity was observed in various proportions of lymphoid cells in both reactive and malignant lymphoid bone marrow aggregates. The percentage of bcl-2 positive cells in malignant aggregates was substantially higher (mean value 78%) than that observed in reactive nodules (mean value 60%). The presence of bcl-2 protein has been confirmed both in malignant and benign bone marrow lymphoid aggregates. Thus, the bcl-2 protein expression should not be used as a discriminating criterion for the malignant nature of lymphoid aggregates.
Gen Diagn Pathol 1996 May
PMID:Expression of bcl-2 protein in distinguishing benign from malignant lymphoid aggregates in bone marrow biopsies. 878 Sep 36

Experimental inoculation of sheep with bovine leukaemia virus (BLV), a retrovirus homologous to the human T-lymphotropic virus type 1 (HTLV-1), induces a chronic expansion of the B lymphocyte population (persistent lymphocytosis) and the development of a B cell leukaemia/lymphosarcoma syndrome. To gain insight into the mechanisms of BLV-induced lymphocytosis, we tested B cell survival capacity and cycling activity in peripheral blood mononuclear cells (PBMCs) from lymphocytotic, asymptomatic and control sheep. Interestingly, B cells from lymphocytotic sheep presented a lower level of spontaneous apoptosis (29%) in ex vivo cultures compared to that obtained with infected asymptomatic (42%) and control (57%/o) sheep PBMCs. Virus capsid (CA) synthesis was mainly found among surviving B cells and the percentage of CA-producing B cells correlated with the extent of B cell survival, indicating that BLV replication in B lymphocytes may promote protection from cell death. B cell survival was not linked with increases in expression of Bcl-2 mRNA or membrane leukosialin (CD43), although both are documented to be involved in some aspects of the B cell life-span. Finally, cell cycle analyses in freshly isolated PBMCs from lymphocytotic sheep revealed a slightly increased proportion of B cells in S phase compared to controls. Altogether, these data suggest that both BLV-induced B cell proliferation and extended survival are involved in the lymphocytotic stage encountered in BLV infection in sheep.
J Gen Virol 1997 Jan
PMID:Bovine leukaemia virus-induced lymphocytosis in sheep is associated with reduction of spontaneous B cell apoptosis. 901 Feb 99

The Epstein-Barr virus latent membrane protein 1 (LMP-1) is essential for virus-induced B cell immortalization and can protect B lymphoma cell lines from apoptosis signals in vitro via induction of cellular Bcl-2 expression. However, we have reported that high-level expression of LMP-1 in epithelial cells (RHEK-1 cells) itself induces apoptosis. This apoptotic event occurs in the absence of detectable Bcl-2 expression in the LMP-1-transfected epithelial cells. In this study, we transfected the bcl-2 gene into the LMP-1-containing cells and examined the effect of Bcl-2 upon LMP-1-mediated apoptosis, and upon the growth phenotype of the transfected cells. The results show that ectopic expression of Bcl-2 specifically blocks apoptotic death induced by LMP-1. This was observed from cell culture viability and from gel electrophoresis and flow cytometric assays of the degree of DNA fragmentation in cultured cells. Furthermore, co-expression of LMP-1 and Bcl-2 in RHEK-1 cells enabled the cells to grow under low-serum conditions and to form colonies in semi-soft agar medium. These results suggest, therefore, that these two proteins play important complementary roles in the process of EBV-associated epithelial cell transformation. It appears significant, therefore, that LMP-1 and Bcl-2 are frequently co-expressed in the malignant cells of an EBV-positive epithelial tumour, nasopharyngeal carcinoma.
J Gen Virol 1997 Nov
PMID:Cooperative interaction between Bcl-2 and Epstein-Barr virus latent membrane protein 1 in the growth transformation of human epithelial cells. 936 85

BHRF 1, a component of the restricted early antigen (EA) complex of the Epstein-Barr virus (EBV) lytic cycle, encodes a 17 kDa putative transmembrane protein with both sequence and functional homology to the Bcl-2 proto-oncogene. To determine whether there was any sequence variation over the BHRF1 open reading frame (ORF), 15 EBV isolates from different geographical regions and from both healthy donors and patients with EBV-associated diseases were sequenced. A small number of base changes which resulted in amino acid substitutions in the BHRF1 protein were found relative to the prototype B95.8 EBV sequence and these were predominantly clustered near the amino terminus of the BHRF1 protein outside conserved domains identified in the Bcl-2 homologues. In transient transfection assays none of the mutations in the BHRF1 ORF from eight different EBV isolates had a significant effect on BHRF1 protein localization compared to the B95.8 BHRF1 protein. However, transient expression of the adenovirus 12 19K protein or Bcl-2 resulted in localization patterns distinct from that observed with BHRF1 protein. Whilst all eight EBV isolates and E1B-19K gave comparable levels of protection to the DNA-damaging agent cis-platin, Bcl-2 did not afford significant protection. Thus, despite several amino acid changes in the BHRF1 ORF of some of the EBV isolates studied, the ability of the protein to protect against cis-platin induced apoptosis is conserved. The highly conserved nature of BHRF1 amongst different EBV isolates at both the sequence and functional level supports the proposed important role of BHRF1 in delaying cell death, thereby maximizing the production of progeny virus and facilitating the establishment of virus persistence.
J Gen Virol 1997 Nov
PMID:BHRF1, a viral homologue of the Bcl-2 oncogene, is conserved at both the sequence and functional level in different Epstein-Barr virus isolates. 936 86

Human herpesvirus-8 (HHV-8) is a gammaherpesvirus that is present primarily in a state of low level persistence in primary effusion lymphoma cell lines. Using BCBL-1 cells that harbour HHV-8 but lack Epstein-Barr virus, we demonstrate that sodium butyrate is much more effective than the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) at inducing high levels of class II and III virus transcription and viral DNA replication, but also initiates apoptosis. Apoptosis occurs prior to assembly of virions when high concentrations of butyrate (1-3 mM) are used, whereas reduction of butyrate concentration to 0.3 mM decreases the rate of apoptosis and results in production and secretion of enveloped virions that are visualized at high number by electron microscopy in approximately 20% of BCBL-1 cells. Butyrate induces much higher levels of multiple class II and class III transcripts than does TPA, including v-MIPI, v-IL-6, v-Bcl-2, vGPCR and ORF26. A decrease in concentration of butyrate from 3 to 0.3 mM delays the peak induction of these genes, but peak levels remain higher than peak levels in response to TPA. These studies indicate that the massive apoptosis induced by 3 mM butyrate could be diminished and delayed by reduction of butyrate concentration to 0.3 mM, thereby allowing expression of high levels of lytic-associated genes and production of high yields of HHV-8 virions.
J Gen Virol 1999 Jan
PMID:Induction of human herpesvirus-8 DNA replication and transcription by butyrate and TPA in BCBL-1 cells. 993 88

Human papillomavirus (HPV) replication occurs in terminally differentiating epithelium, and requires the activation of cellular DNA replication proteins. Unscheduled DNA replication can result in the induction of apoptosis, and the viral E6 protein induces the degradation of p53 to prevent this. It has recently been shown that HPV-18 E6 can also stimulate the degradation of Bak, a pro-apoptotic member of the Bcl-2 family. This report shows that the E6 proteins from HPV-18, HPV-16 and HPV-11 can all bind to Bak in vitro, stimulate its degradation in vivo and reduce Bak-induced apoptosis. However, the non-oncogenic HPV-11 E6 is less effective than the oncogenic E6 proteins in each of these assays, indicating that the ability of HPV to circumvent the apoptosis induced by Bak may contribute to the oncogenic potential of the virus.
J Gen Virol 1999 Jun
PMID:Human papillomavirus (HPV) E6 interactions with Bak are conserved amongst E6 proteins from high and low risk HPV types. 1037 70

Rubella virus (RV) generally causes a mild disease but it is highly teratogenic when infection occurs during the first trimester of gestation. Under in vitro conditions, RV induces characteristic cytopathic changes on several cell lines, e.g. cell detachment from the monolayer and condensation of chromatin. The purpose of this study was to characterize RV-induced cell death and to determine the factors that might be involved in this process. Both acutely and persistently infected cells exhibited alterations characteristic of apoptosis, including DNA fragmentation, annexin V staining and reduced DNA content. UV-inactivated RV did not induce apoptotic cell death and expression of RV structural proteins in a transfected cell line was not sufficient to induce apoptosis, supporting the interpretation that replicating virus is necessary to provoke apoptosis. Both persistently infected and 24S-transfected cells retained their susceptibility to undergo apoptosis in response to either staurosporine or camptothecin. This indicates that RV does not block chemically induced apoptosis. The signals involved in RV-associated apoptosis appear to be independent of p53 and of the Bcl-2 gene family.
J Gen Virol 1999 Jul
PMID:Rubella virus-induced cytopathic effect in vitro is caused by apoptosis. 1042 33

Transcription of the human polyomavirus JC virus (JCV) genome is regulated by cellular proteins and the large tumour (T) antigen. Earlier studies led to the identification of nuclear factor-1 (NF-1)-binding sites in the JCV enhancer by DNase I protection assays of extracts from retinoic acid (RA)-differentiated P19 embryonal carcinoma (EC) cells. In this study, a cDNA clone that encodes a protein capable of binding to the JCV NF-1 sites was isolated from an RA-differentiated EC cell cDNA library. Sequence analysis revealed that the cDNA isolated was identical to the previously described Bcl-2-interacting protein BAG-1 (Bcl-2-associated athano gene-1). Results from RNA studies indicated that BAG-1 is expressed in several cell types. Co-transfection of a recombinant BAG-1 expression plasmid with JCV promoters indicated that BAG-1 stimulates transcription of the JCV(E) promoter and to a lesser extent the JCV(L) promoter. Mutations in the NF-1 sites in the JCV(E) promoter eliminated the activation by BAG-1. Thus, BAG-1 is a novel transcription factor that may play a role in JCV expression.
J Gen Virol 2000 Feb
PMID:BAG-1, a novel Bcl-2-interacting protein, activates expression of human JC virus. 1064 33

Apoptosis (programmed cell death) is an important process participating in the formation of organs and tissues during embryogenesis. Our aim of the work is studying the role of the apoptosis during the human embryonic differentiation. We tend to give acquired findings into the correlation with expression of proteins Bcl-2 and Bax (products of genes regulating apoptosis). Detection of the apoptosis was carried out on 25 routinely processed human embryos by means of TUNEL technique. The level of expression of Bcl-2 and Bax was determined using standard three-step immunohistochemical procedure. Results were achieved by the comparison of apoptoic index and the level expression of Bcl-2 and Bax was semiquantitatively evaluated. The low value of apoptotic index was mostly accompanied by the high expression of Bcl-2 and the Bax expression was not proportionally related to the value of apoptic index.
Gen Physiol Biophys 1999 Dec
PMID:The role of the apoptosis and the genes regulating apoptosis in the early differentiation of human embryo. 1070 50


1 2 3 4 5 6 7 Next >>