![]() ![]() The small and large T antigens result from this. This results in an mRNA that is spliced into two segments. Inside the cell nucleus, the cellular RNA polymerase II acts to promote early gene expression. Penetration into the cell is through a caveolin vesicle. The virion adheres to cell surface receptors of MHC class I by the virion glycoprotein VP1. SV40 consists of an unenveloped icosahedral virion with a closed circular double-stranded DNA genome of 5.2 kb. A mutated p53 gene may contribute to uncontrolled cellular proliferation, leading to a tumor. Tumor suppressor p53 is responsible for initiating regulated cell death (" apoptosis"), or cell cycle arrest when a cell is damaged. The mechanism may involve suppression of the transcriptional properties of tumor suppressor p53 in humans by the SV40 large T antigen and SV40 small T-antigen. SV40 may act as a co-carcinogen with crocidolite asbestos to cause mesothelioma. This 2004 announcement is in contrast to a 2002 study performed by The National Academy of Sciences Immunization Safety Review committee that stated, "The committee concludes that the biological evidence is moderate that SV40 exposure could lead to cancer in humans under natural conditions". This announcement was based on two studies. The US National Cancer Institute announced in 2004 that although SV40 does cause cancer in some animal models, "substantial epidemiological evidence has accumulated to indicate that SV40 likely does not cause cancer in humans". As a result of these uncertainties, academic opinion remains divided, with some arguing that this hypothesis is not supported by the data and others arguing that some cancers may involve SV40. It is currently unclear whether SV40 has any role in causing tumors. The identities of the cellular proteins in the complex with pmT-ag are unknown, although one member (56K) is recognized by p53-specific monoclonal antibodies.The hypothesis that SV40 might cause cancer in humans has been a particularly controversial area of research. The characteristics of growth-dependent expression and rapid turnover rate suggest a functional role for the membrane complex. The complex exhibited a highly dynamic association with the cell membrane, as demonstrated by pulse-chase analysis. The growth state of the cells markedly influenced the expression of the T-ag-containing surface complexes more complexes were recovered from actively dividing cells than from confluent cell cultures, and suspension cells yielded more complexes than cells on a substratum. Both amino- and carboxylterminal T-ag-specific monoclonal antibodies co-precipitated T-ag and the 35-60K Mr proteins, but antibodies against the internal portion of T-ag precipitated only uncomplexed T-ag. A non-cytolytic protein extraction technique utilizing 1-butanol solubilized from SV40-transformed cells a multimeric complex composed of pmT-ag and at least five cellular proteins ranging in size from 35,000 (35K) to 60K M. Nuclear-transport-defective mutants of T-ag can transform established cells in culture, but not primary cells, suggesting that non-nuclear forms of T-ag may mediate some transformation-related process(es). The disposition of T-ag in the membrane exposes both the amino and the carboxyl terminus on the exterior of the cell. Transport to the cell surface is by an unknown mechanism that does not involve the secretory pathway. The pmT-ag population is structurally very similar to the nT-ag. SV40 T-antigen (T-ag) is localized in both the nucleus (nT-ag) and plasma membrane (pmT-ag) of cells and provides multiple functions necessary for cell transformation. ![]()
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