Disease relevance of HpVgp1

• Host range and cell cycle activation properties of polyomavirus large T-antigen mutants defective in pRB binding [1].
• RESULTS: Most animals expressing wild-type large T antigen developed pancreatic insulinomas and lymphomas and died between 3 and 6 months of age [2].
• Interaction of retinoblastoma protein family members with large T-antigen of primate polyomaviruses [3].
• Large T antigen is responsible for both viral and cellular transcriptional regulation, virion assembly, viral DNA replication, and alteration of the cell cycle [4].
• Large T antigen is the replicative helicase of simian virus 40 [5].

High impact information on HpVgp1

• Cells transformed by Polyoma virus (Py) can undergo a high rate of excision or amplification of integrated viral DNA sequences, and these phenomena require the presence of homology (i.e., repeats) within the viral insertion as well as a functional viral large T antigen (T-Ag) [6].
• Phosphorylation is not diminished in extracts of polyoma tsA mutant-infected cells shifted to the nonpermissive temperature late in infection, conditions which inactivate the large T antigen [7].
• In contrast, large T antigen alone is sufficient to induce tumors in the endocrine pancreas and thymus [2].
• Large T antigen on the simian virus 40 origin of replication: a 3D snapshot prior to DNA replication [5].
• By using micro-positron-emission tomography, interactions between p53 tumor suppressor and the large T antigen of simian virus 40 were visualized in tumor xenografts of HeLa cells stably transfected with the imaging constructs [8].

Chemical compound and disease context of HpVgp1

• Polyomavirus large T antigen coprecipitates with p53 phosphorylated on serine 18 and also with p21Cip1/WAF1 [9].

Biological context of HpVgp1

• The most polymorphic coding region in the viral genome is VP1, but significant variation is also present in the large T-antigen gene, wherein polymorphisms are found in 11.39% of all nucleotide sites, 46.22% of which are cluster specific [10].
• We have examined the growth properties of polyomavirus large T-antigen mutants that are unable to bind pRB, the product of the retinoblastoma tumor suppressor gene [1].
• The carboxyl-terminal domain of large T antigen rescues SV40 host range activity in trans independent of acetylation [11].
• Our results are compatible with the hypothesis that large T antigen destabilizes the cellular genome, and that specific mutations arising from this process may contribute to cell immortalization [12].
• This recombinant plasmid, pSV01, binds to a purified T antigen in vitro and replicates in monkey cells when supplied with large T antigen [13].

Anatomical context of HpVgp1

• Both cell lines were found to produce truncated large T antigen and entire middle and small T antigens [14].
• Umbilical cord endothelial cells expressing large T antigen: comparison with primary cultures and effect of cell age [15].
• Infection of primary human prostate epithelial cells with BK polyomavirus dramatically induced Dnmt1 transcription following large T antigen (TAg) translation and E2F activation [16].
• When grown in 100 microM Zn2+, transformed myocytes expressed the large T antigen, divided rapidly, and acquired an apparently unlimited proliferative capacity [17].
• Correspondence re: F. Martini et al., SV40 early region and large T antigen in human brain tumors, peripheral blood cells, and sperm fluids from healthy individuals. Cancer Res., 56: 4820-4825, 1996 [18].

Associations of HpVgp1 with chemical compounds

• The viral large T antigen bound to Janus tyrosine kinase 1 and inactivated signaling through IFN receptors [19].
• Large T antigen of SV40 interacts with p53, pRb/p107/p130 family members, and the cyclic AMP-responsive element-binding protein (CREB)-binding protein (CBP)/p300 [20].
• Thus the loss of the growth inhibitory effect of vitamin D3 in HBL100 cells may be caused by the expression of the large T antigen in the cells, and provide further evidence that VDR is required for efficient growth inhibition by vitamin D3 [21].
• Only 2 cases showed strong/diffuse and moderate/focal staining for LTag with both representing invasive high-grade urothelial carcinoma (where no inclusions were seen on hematoxylin and eosin-stained sections) and both demonstrating positive immunostaining for p53 [22].
• Sodium butyrate treatment did, however, result in the appearance of a new nuclear protein which bound specifically to a SV40 promoter fragment containing large-T antigen binding sites I and II [23].

Analytical, diagnostic and therapeutic context of HpVgp1

• Immunocytochemistry revealed that > 95% of the cells express the large T-antigen at both temperatures [24].
• Gene targeting in rat embryo fibroblasts promoted by the polyomavirus large T antigen [25].
• We have established an assay to detect JC viral DNA in brain tissue and CSF of patients with progressive multifocal leukoencephalopathy (PML) and amplified a 106-base pair segment of the gene encoding JC viral large T antigen by polymerase chain reaction (PCR) from the brains of eight patients with PML and from one of six CSF samples [26].
• Large T antigen obtained from a simian virus 40-transformed human cell line either by immunoprecipitation or by standard preparatory methods migrated like a 94,000-molecular-weight (approximately 94K) polypeptide in SDS-gels but was found to have an approximate was observed with T antigen obtained from lytically infected monkey cells [27].
• ALM is, however, unaffected in early gene expression as measured both by indirect immunofluorescence of large T antigen and by transformation levels of rat F-111 cells [28].

References