polyomavirus transforming antigens

Summary

Summary: Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.

Top Publications

  1. Valle M, Chen X, Donate L, Fanning E, Carazo J. Structural basis for the cooperative assembly of large T antigen on the origin of replication. J Mol Biol. 2006;357:1295-305 pubmed
    ..This mechanism provides the structural basis for the cooperative assembly of LTag double hexamer on the cognate viral ori. ..
  2. Williams T, Hassan G, Li J, Cohen A, Medina F, Frank P, et al. Caveolin-1 promotes tumor progression in an autochthonous mouse model of prostate cancer: genetic ablation of Cav-1 delays advanced prostate tumor development in tramp mice. J Biol Chem. 2005;280:25134-45 pubmed
    ..Our current findings provide the first in vivo molecular genetic evidence that Cav-1 does indeed function as a tumor promoter during prostate carcinogenesis, rather than as a tumor suppressor. ..
  3. Feng H, Shuda M, Chang Y, Moore P. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science. 2008;319:1096-100 pubmed publisher
    ..Thus, MCV may be a contributing factor in the pathogenesis of MCC...
  4. Moreno C, Ramachandran S, Ashby D, Laycock N, Plattner C, Chen W, et al. Signaling and transcriptional changes critical for transformation of human cells by simian virus 40 small tumor antigen or protein phosphatase 2A B56gamma knockdown. Cancer Res. 2004;64:6978-88 pubmed
    ..Our data support a model in which ST promotes survival through constitutive integrin signaling, src phosphorylation, and nuclear factor kappaB activation, while inhibiting cell-cell adhesion pathways. ..
  5. Wikstrom P, Lindahl C, Bergh A. Characterization of the autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) as a model to study effects of castration therapy. Prostate. 2005;62:148-64 pubmed
    ..This model can preferably be used to elucidate how this treatment works, and to test how it can be improved by additional therapies. ..
  6. Podsypanina K, Du Y, Jechlinger M, Beverly L, Hambardzumyan D, Varmus H. Seeding and propagation of untransformed mouse mammary cells in the lung. Science. 2008;321:1841-4 pubmed publisher
    ..Mammary cells lacking oncogenic transgenes displayed a similar capacity for long-term residence in the lungs but did not form ectopic tumors...
  7. Matsumura T, Takesue M, Westerman K, Okitsu T, Sakaguchi M, Fukazawa T, et al. Establishment of an immortalized human-liver endothelial cell line with SV40T and hTERT. Transplantation. 2004;77:1357-65 pubmed
    ..This study demonstrates the utility and efficiency of the reversible immortalization procedure to expand primary human LECs for basic studies. ..
  8. Gai D, Zhao R, Li D, Finkielstein C, Chen X. Mechanisms of conformational change for a replicative hexameric helicase of SV40 large tumor antigen. Cell. 2004;119:47-60 pubmed
    ..Additionally, six unique beta hairpins on the channel surface move longitudinally along the central channel, possibly serving as a motor for pulling DNA into the LTag double hexamer for unwinding. ..
  9. White M, Khalili K. Interaction of retinoblastoma protein family members with large T-antigen of primate polyomaviruses. Oncogene. 2006;25:5286-93 pubmed
    ..In the context of cellular transformation and tumorigenesis, T-antigen/pRB interaction is an indispensable event. ..

More Information

Publications62

  1. Kandori H, Suzuki S, Asamoto M, Murasaki T, Mingxi T, Ogawa K, et al. Influence of atrazine administration and reduction of calorie intake on prostate carcinogenesis in probasin/SV40 T antigen transgenic rats. Cancer Sci. 2005;96:221-6 pubmed
    ..Our results indicate that the observed atrazine-related suppression of prostate carcinogenesis was probably caused by the decrease in calorie intake, rather than by atrazine-related endocrine disruption. ..
  2. Liu R, Varghese S, Rabkin S. Oncolytic herpes simplex virus vector therapy of breast cancer in C3(1)/SV40 T-antigen transgenic mice. Cancer Res. 2005;65:1532-40 pubmed
    ..When the first mammary tumor was treated and the remaining mammary glands removed, NV1042 was more efficacious than G47Delta at inhibiting the growth and progression of injected tumors. ..
  3. Zeng Y, Yokohira M, Saoo K, Takeuchi H, Chen Y, Yamakawa K, et al. Inhibition of prostate carcinogenesis in probasin/SV40 T antigen transgenic rats by raloxifene, an antiestrogen with anti-androgen action, but not nimesulide, a selective cyclooxygenase-2 inhibitor. Carcinogenesis. 2005;26:1109-16 pubmed
  4. Poulin D, Kung A, DeCaprio J. p53 targets simian virus 40 large T antigen for acetylation by CBP. J Virol. 2004;78:8245-53 pubmed
    ..T Ag acetylation may provide a regulatory mechanism for T Ag binding to a cellular factor or play a role in another aspect of T Ag function. ..
  5. Uramoto H, Hackzell A, Wetterskog D, Ballági A, Izumi H, Funa K. pRb, Myc and p53 are critically involved in SV40 large T antigen repression of PDGF beta-receptor transcription. J Cell Sci. 2004;117:3855-65 pubmed
    ..However, LT binds the promoter in the absence of pRb and p53 in Saos-2 cells stably expressing LT. These results suggest that LT binds the promoter and interferes with NF-Y and Sp1 to repress it in the presence of Myc, pRb and p53. ..
  6. Ahuja D, Sáenz Robles M, Pipas J. SV40 large T antigen targets multiple cellular pathways to elicit cellular transformation. Oncogene. 2005;24:7729-45 pubmed
  7. Spence S, Shaffer A, Staudt L, Amde S, Manney S, Terry C, et al. Transformation of late passage insulin-like growth factor-I receptor null mouse embryo fibroblasts by SV40 T antigen. Cancer Res. 2006;66:4233-9 pubmed
    ..We conclude that late passage IGF-I receptor null mouse embryo fibroblasts can be transformed by SV40 T antigen, and that ErbB-3 may play a role in permitting transformation by T antigen. ..
  8. DeAngelis T, Chen J, Wu A, Prisco M, Baserga R. Transformation by the simian virus 40 T antigen is regulated by IGF-I receptor and IRS-1 signaling. Oncogene. 2006;25:32-42 pubmed
    ..We propose that the requirement for a tyrosyl-phosphorylated IRS-1 provides a mechanism to explain the failure of T antigen to transform MEFs with deleted IGF-IR genes. ..
  9. Kaur S, Greaves P, Cooke D, Edwards R, Steward W, Gescher A, et al. Breast cancer prevention by green tea catechins and black tea theaflavins in the C3(1) SV40 T,t antigen transgenic mouse model is accompanied by increased apoptosis and a decrease in oxidative DNA adducts. J Agric Food Chem. 2007;55:3378-85 pubmed
    ..05%) were reduced by 78 (p<0.001) or 63% (p<0.05), respectively, as compared to controls. The results render the exploration of the breast cancer chemopreventive properties of tea preparations in humans worthwhile. ..
  10. Verschoyle R, Brown K, Steward W, Gescher A. Consumption of silibinin, a flavonolignan from milk thistle, and mammary cancer development in the C3(1) SV40 T,t antigen transgenic multiple mammary adenocarcinoma (TAg) mouse. Cancer Chemother Pharmacol. 2008;62:369-72 pubmed
    ..Intervention neither promoted, nor interfered with, tumour development. The result suggests that promotion of carcinogenesis is not a feature of silibinin consistent across rodent models of mammary carcinogenesis. ..
  11. Leong H, Mathur P, Greene G. Inhibition of mammary tumorigenesis in the C3(1)/SV40 mouse model by green tea. Breast Cancer Res Treat. 2008;107:359-69 pubmed
    ..Our data strongly support the potential use of green tea as a breast cancer chemopreventive agent. ..
  12. Li D, Zhao R, Lilyestrom W, Gai D, Zhang R, DeCaprio J, et al. Structure of the replicative helicase of the oncoprotein SV40 large tumour antigen. Nature. 2003;423:512-8 pubmed
  13. Cho Y, Takahashi S, Asamoto M, Suzuki S, Inaguma S, Hokaiwado N, et al. Age-dependent histopathological findings in the prostate of probasin/SV40 T antigen transgenic rats: lack of influence of carcinogen or testosterone treatment. Cancer Sci. 2003;94:153-7 pubmed
    ..These results suggest that our TG rats are suitable for clarification of mechanisms in early stages of prostate carcinogenesis, that is, from prostatic intraepithelial neoplasia (PIN) to non-invasive and then invasive lesions. ..
  14. Valls E, de la Cruz X, Martínez Balbás M. The SV40 T antigen modulates CBP histone acetyltransferase activity. Nucleic Acids Res. 2003;31:3114-22 pubmed
    ..These findings highlight the importance of histone acetylation in the regulation of the cell cycle by oncoviral proteins. ..
  15. Wu Y, Cui K, Miyoshi K, Hennighausen L, Green J, Setser J, et al. Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors. Cancer Res. 2003;63:4384-8 pubmed
    ..Our data demonstrate that circulating IGF-I levels play a significant role as a risk factor in the onset and development of mammary tumors in two well-established animal models of breast cancer. ..
  16. Velicescu M, Yu J, Herbert B, Shay J, Granada E, Dubeau L. Aneuploidy and telomere attrition are independent determinants of crisis in SV40-transformed epithelial cells. Cancer Res. 2003;63:5813-20 pubmed
    ..Reestablishment or emergence of ploidy stability, which is not always dependent on telomerase activation, is necessary for acquisition of the potential to achieve replicative immortality...
  17. Dilworth S. Polyoma virus middle T antigen and its role in identifying cancer-related molecules. Nat Rev Cancer. 2002;2:951-6 pubmed
    ..However, how many know that a small DNA mouse virus was crucial in establishing both of these tenets? ..
  18. Zheng X, Gao J, Zhang H, Geiger T, Liu Y, Zheng P. Clonal deletion of simian virus 40 large T antigen-specific T cells in the transgenic adenocarcinoma of mouse prostate mice: an important role for clonal deletion in shaping the repertoire of T cells specific for antigens overexpressed in solid tumor. J Immunol. 2002;169:4761-9 pubmed
  19. Lewis B, Klimstra D, Varmus H. The c-myc and PyMT oncogenes induce different tumor types in a somatic mouse model for pancreatic cancer. Genes Dev. 2003;17:3127-38 pubmed
    ..Our model appears to be useful for elucidating the genetic alterations, target cells, and signaling pathways that are important in the genesis of different types of pancreatic cancer...
  20. Desai K, Xiao N, Wang W, Gangi L, Greene J, Powell J, et al. Initiating oncogenic event determines gene-expression patterns of human breast cancer models. Proc Natl Acad Sci U S A. 2002;99:6967-72 pubmed
    ..Moreover, similarities in gene expression between human breast cancers and the mouse models have been identified, thus providing an important component for the validation of transgenic mammary cancer models. ..
  21. Calvo A, Feldman A, Libutti S, Green J. Adenovirus-mediated endostatin delivery results in inhibition of mammary gland tumor growth in C3(1)/SV40 T-antigen transgenic mice. Cancer Res. 2002;62:3934-8 pubmed
    ..Our results demonstrate that the adenoviral induction of high levels of circulating endostatin significantly inhibits mammary tumor growth during the period when the "angiogenic switch" occurs. ..
  22. Quintana S, Venara M, Rey R, di Clemente N, Chemes H. Origin and evolution of somatic cell testicular tumours in transgenic mice. J Pathol. 2010;221:443-51 pubmed publisher
  23. Reed M, Karres N, Eyman D, Cruz A, Brekken R, Plymate S. The effects of aging on tumor growth and angiogenesis are tumor-cell dependent. Int J Cancer. 2007;120:753-60 pubmed
    ..These data demonstrate that tumor-cell specific features determine the effect of aging on tumor growth and angiogenesis. ..
  24. Chen L, Wang X, Fluck M. Independent contributions of polyomavirus middle T and small T to the regulation of early and late gene expression and DNA replication. J Virol. 2006;80:7295-307 pubmed
    ..This connection explains the pleiotropy of MT and ST effects on transcription and DNA replication. ..
  25. Gordon G, Lambert Q, Daniel K, Reuther G. Transforming JAK1 mutations exhibit differential signalling, FERM domain requirements and growth responses to interferon-?. Biochem J. 2010;432:255-65 pubmed publisher
    ..Our characterization of these novel mutations contributes to a better understanding of mutational activation of JAK1. ..
  26. Tong C, Howard S, Shah H, Van Quill K, Lin E, Grossniklaus H, et al. Effects of celecoxib in human retinoblastoma cell lines and in a transgenic murine model of retinoblastoma. Br J Ophthalmol. 2005;89:1217-20 pubmed
    ..On the basis of these findings, oral celecoxib therapy is unlikely to have clinical utility in the treatment of retinoblastoma. ..
  27. Vasiljeva O, Papazoglou A, Krüger A, Brodoefel H, Korovin M, Deussing J, et al. Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer. Cancer Res. 2006;66:5242-50 pubmed
    ..These results indicate that both cancer cell-derived and stroma cell-derived (i.e., macrophages) CTSB plays an important role in tumor progression and metastasis. ..
  28. Willimsky G, Blankenstein T. Sporadic immunogenic tumours avoid destruction by inducing T-cell tolerance. Nature. 2005;437:141-6 pubmed
    ..Furthermore, in the primary host tumour-induced tolerance is associated with the expansion of non-functional T cells. Together, our data argue against immunosurveillance of spontaneous cancer. ..
  29. Lowe D, Shearer M, Jumper C, Bright R, Kennedy R. Fc gamma receptors play a dominant role in protective tumor immunity against a virus-encoded tumor-specific antigen in a murine model of experimental pulmonary metastases. J Virol. 2007;81:1313-8 pubmed
    ..Additionally, these data demonstrate the potential utility of ADCC as a viable approach for targeting vaccination strategies that promote FcgammaRI/III scavenging pathways against cancer. ..
  30. Berntzen G, Lunde E, Flobakk M, Andersen J, Lauvrak V, Sandlie I. Prolonged and increased expression of soluble Fc receptors, IgG and a TCR-Ig fusion protein by transiently transfected adherent 293E cells. J Immunol Methods. 2005;298:93-104 pubmed
    ..The approach should be of interest to laboratories that do not have access to a bioreactor but still have a requirement for reasonable amounts of protein to be produced in an easy and cost-effective manner. ..
  31. Valls E, Blanco García N, Aquizu N, Piedra D, Estarás C, de la Cruz X, et al. Involvement of chromatin and histone deacetylation in SV40 T antigen transcription regulation. Nucleic Acids Res. 2007;35:1958-68 pubmed
    ..These findings highlight the importance of the histone acetylation/deacetylation balance in the cellular transformation mediated by oncoviral proteins. ..
  32. Shen Q, Sun Q, Wei X, Dong J, Zhang R, Wu P, et al. Generation and characterization of islet cell tumor in pTet-on/pTRE-SV40Tag double-transgenic mice model. J Biosci Bioeng. 2007;104:14-21 pubmed
    ..The results suggest that a Tag transgenic mice model could be used to study the molecular mechanism of the tumorigenesis of islets. ..
  33. Klucky B, Koch B, Radolf M, Steinlein P, Wintersberger E. Polyomavirus tumorantigens have a profound effect on gene expression in mouse fibroblasts. Oncogene. 2004;23:4707-21 pubmed
    ..In fact, some genes are transactivated by LT as well as ST completely independent of an interaction with their major cellular targets, pocket proteins and PP2A, respectively. ..
  34. Kim M, Bellini M, Ceman S. Fragile X mental retardation protein FMRP binds mRNAs in the nucleus. Mol Cell Biol. 2009;29:214-28 pubmed publisher
    ..Collectively, our data provide the first lines of evidence that FMRP binds mRNA in the nucleus. ..
  35. Schaffhausen B, Roberts T. Lessons from polyoma middle T antigen on signaling and transformation: A DNA tumor virus contribution to the war on cancer. Virology. 2009;384:304-16 pubmed publisher
    ..There remain many opportunities as we seek a full molecular understanding of MT and apply some of its lessons to human cancer...
  36. Khopde S, Simmons D. Simian virus 40 DNA replication is dependent on an interaction between topoisomerase I and the C-terminal end of T antigen. J Virol. 2008;82:1136-45 pubmed
    ..These residues are located on the back edges of the T-antigen double hexamer. We propose that topo I binds to one site on each hexamer to permit the initiation of SV40 DNA replication. ..
  37. Lin E, Kemball C, Hadley A, Wilson J, Hofstetter A, Pack C, et al. Heterogeneity among viral antigen-specific CD4+ T cells and their de novo recruitment during persistent polyomavirus infection. J Immunol. 2010;185:1692-700 pubmed publisher
  38. Sumino Y, Hirata Y, Sato F, Mimata H. Growth mechanism of satellite cells in human urethral rhabdosphincter. Neurourol Urodyn. 2007;26:552-561 pubmed publisher
    ..These findings may be useful in the development of a novel technique for the regeneration of human RS to treat urinary incontinence. ..
  39. Zhang X, Mehta R, Lantvit D, Coschigano K, Kopchick J, Green J, et al. Inhibition of estrogen-independent mammary carcinogenesis by disruption of growth hormone signaling. Carcinogenesis. 2007;28:143-50 pubmed
  40. Sun B, Chen M, Hawks C, Hornsby P, Wang X. Tumorigenic study on hepatocytes coexpressing SV40 with Ras. Mol Carcinog. 2006;45:213-9 pubmed
  41. Mogha A, Fautrel A, Mouchet N, Guo N, Corre S, Adamski H, et al. Merkel cell polyomavirus small T antigen mRNA level is increased following in vivo UV-radiation. PLoS ONE. 2010;5:e11423 pubmed publisher
    ..These findings demonstrate that solar radiation has an impact on MCPyV mRNA levels that may explain the association between MCC and solar exposure. ..
  42. Hattori Y, Kanamoto N, Kawano K, Iwakura H, Sone M, Miura M, et al. Molecular characterization of tumors from a transgenic mouse adrenal tumor model: comparison with human pheochromocytoma. Int J Oncol. 2010;37:695-705 pubmed
    ..This mouse model would be a useful tool for the development of anti-cancer drugs and for understanding the etiology of adrenal neuroblastoma. ..
  43. Lu X, Arbiser J, West J, Hoedt Miller M, Sheridan A, Govindarajan B, et al. Tumor necrosis factor-related apoptosis-inducing ligand can induce apoptosis in subsets of premalignant cells. Am J Pathol. 2004;165:1613-20 pubmed
    ..These results suggest that TRAIL can induce apoptosis in premalignant cells and suggests a novel therapy for the treatment of premalignant lesions in vivo. ..
  44. Tye B, Chang V. Dual functional regulators coordinate DNA replication and gene expression in proliferating cells. Front Biosci. 2004;9:2548-55 pubmed
    ..Emerging examples in eukaryotes are the growth responsive transcription factor E2f, the MADS domain combinatorial transcription factor Mcm1, and a subunit of the MCM2-7 helicase, Mcm7. ..
  45. Fenton K, Mjelle J, Jakobsen S, Olsen R, Rekvig O. Renal expression of polyomavirus large T antigen is associated with nephritis in human systemic lupus erythematosus. Mol Immunol. 2008;45:3117-24 pubmed publisher
    ..Complexes of nucleosomes, T-ag and anti-T-ag and anti-dsDNA antibodies bind glomerular membranes and contribute to the evolution of lupus nephritis in human SLE. ..
  46. Zhang H, Kuang S, Liao L, Zhou S, Xu J. Haploid inactivation of the amplified-in-breast cancer 3 coactivator reduces the inhibitory effect of peroxisome proliferator-activated receptor gamma and retinoid X receptor on cell proliferation and accelerates polyoma middle-T antigen-induced mamm. Cancer Res. 2004;64:7169-77 pubmed
    ..These results suggest that AIB3 may be a tumor suppressor that is required for the inhibition of cell proliferation by PPARgamma and RXR. ..
  47. Egwuagu C, Li W, Yu C, Che Mei Lin M, Chan C, Nakamura T, et al. Interferon-gamma induces regression of epithelial cell carcinoma: critical roles of IRF-1 and ICSBP transcription factors. Oncogene. 2006;25:3670-9 pubmed
  48. Haeryfar S, DiPaolo R, Tscharke D, Bennink J, Yewdell J. Regulatory T cells suppress CD8+ T cell responses induced by direct priming and cross-priming and moderate immunodominance disparities. J Immunol. 2005;174:3344-51 pubmed
    ..Therefore, Treg influence TCD8 immunodominance hierarchies by moderating disparities in responses to different determinants. ..
  49. Khopde S, Roy R, Simmons D. The binding of topoisomerase I to T antigen enhances the synthesis of RNA-DNA primers during simian virus 40 DNA replication. Biochemistry. 2008;47:9653-60 pubmed publisher
    ..It is also shown that topo I has the ability to bind to human RPA directly, suggesting that the stimulation of pol/prim activity may be mediated in part through RPA in the DNA synthesis initiation complex...
  50. Harper C, Patel B, Cook L, Wang J, Shirai T, Eltoum I, et al. Characterization of SV-40 Tag rats as a model to study prostate cancer. BMC Cancer. 2009;9:30 pubmed publisher
  51. Kowolik C, Liang S, Yu Y, Yee J. Cre-mediated reversible immortalization of human renal proximal tubular epithelial cells. Oncogene. 2004;23:5950-7 pubmed
    ..Thus, reversible immortalization allows the expansion of human RPTECs, leading to large production of RPTECs that retain most tissue-specific properties. ..
  52. Huh J, Calvo A, Stafford J, Cheung M, Kumar R, Philp D, et al. Inhibition of VEGF receptors significantly impairs mammary cancer growth in C3(1)/Tag transgenic mice through antiangiogenic and non-antiangiogenic mechanisms. Oncogene. 2005;24:790-800 pubmed
  53. Cecena G, Wen F, Cardiff R, Oshima R. Differential sensitivity of mouse epithelial tissues to the polyomavirus middle T oncogene. Am J Pathol. 2006;168:310-20 pubmed
    ..The variety of responses of different epithelia to PyMT demonstrates the importance of the differentiated state in interpreting oncogenic signals. ..