Hepatic Expression of SV40 Small-t Antigen Blocks the in Vivo CD95-Mediated Apoptosis

Gillet, Reynald; Cavard, Catherine; Grimber, G.; Briand, Pascale; Joulin, Virginie

doi:10.1006/bbrc.2001.4988

Cited by 10 publications

(8 citation statements)

References 46 publications

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“…Moreover, our findings provide in vivo evidence supporting HGF/Akt signaling in association with SV40 Tag expression in primary malignant mesotheliomas. A correlation of SV40, Akt activity, and CD95/ Fas receptor down-regulation has already been reported (24,25). Our data show that Akt activity inhibits CD95 overexpression subsequent to DNA damage by the chemotherapeutic agent VP-16, providing a mechanistic link with the observed antiapoptotic effect.…”

Section: Discussionsupporting

confidence: 79%

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SV40-Dependent AKT Activity Drives Mesothelial Cell Transformation after Asbestos Exposure

et al. 2005

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Human malignant mesothelioma is an aggressive cancer generally associated with exposure to asbestos, although SV40 virus has been involved as a possible cofactor by a number of studies. Asbestos fibers induce cytotoxicity in human mesothelial cells (HMC), although cell survival activated by key signaling pathways may promote transformation. We and others previously reported that SV40 large T antigen induces autocrine loops in HMC and malignant mesothelioma cells, leading to activation of growth factor receptors. Now we show that SV40 induces cell survival via Akt activation in malignant mesothelioma and HMC cells exposed to asbestos. Consequently, prolonged exposure to asbestos fibers progressively induces transformation of SV40-positive HMC. As a model of SV40/asbestos cocarcinogenesis, we propose that malignant mesothelioma originates from a subpopulation of transformed stem cells and that Akt signaling is a novel therapeutic target to overcome malignant mesothelioma resistance to conventional therapies. (Cancer Res 2005; 65(12): 5256-62)

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Section: Discussionsupporting

confidence: 79%

“…Previous work has shown that expression of the SV40 genome, or of Tag-encoding sequences, increases apoptosis resistance in various cell types (17,(23)(24)(25). Expression of recombinant Tag in human malignant mesothelioma cells exerts an antiapoptotic effect, which is reverted by Tag antisense RNA (26).…”

Section: Discussionmentioning

confidence: 99%

SV40-Dependent AKT Activity Drives Mesothelial Cell Transformation after Asbestos Exposure

et al. 2005

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“…For POLST, opposite effects are obtained depending on whether cells are growing in serum-containing medium or are serum starved (2). SVST can also be apoptotic (21), but SVST promoted survival in MDA-MB231 cells (29) or hepatocytes (20). The ability of POLST and SVST to regulate cell survival is connected to interaction with PP2A.…”

Section: Discussionmentioning

confidence: 99%

“…POLST can protect against serum starvation-induced apoptosis (2) and resists the effects of p53-induced apoptosis (54). SVST opposes apoptosis induced by LT (37) or CD95 (20). Both POLST (2) and SVST (21) can also be proapoptotic under some circumstances.…”

mentioning

confidence: 98%

Comparisons between Murine Polyomavirus and Simian Virus 40 Show Significant Differences in Small T Antigen Function

Andrabi

Hwang

Choe

et al. 2011

J Virol

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DNA tumor viruses of the polyomavirus family have helped us understand important cellular processes, particularly those associated with the signal transduction of cell cycle regulation and transformation. For example, polyomavirus middle T antigen (PyMT) studies were crucial to the discovery of the importance of tyrosine phosphorylation (17) and phosphatidylinositol 3-kinase (PI3) kinase activity (70) in cellular signaling. Comparative studies of the individual members of the polyomavirus family have also been very informative. For example, p53 was discovered as a protein that associates with simian virus 40 (SV40) large T antigen (LT) (38, 39). Comparison of SV40 LT that binds p53 and transforms cells to polyomavirus LT (PyLT) that does neither of these focused attention on the role of p53 in cell cycle regulation.All members of the polyomavirus family produce a small T antigen (ST) as one of the early gene products. Polyomavirus small T antigen (POLST) and SV40 small T antigen (SVST) share many structural similarities with each other (Fig. 1). Both have an N-terminal J domain with a conserved HP DKGG motif that can bind heat shock proteins, and both possess zinc-binding cysteine motifs. Both POLST and SVST bind and perturb protein phosphatase 2A (PP2A) (51). PP2A functions as a trimeric ABC complex, where the scaffolding A subunit binds a catalytic subunit (C) and some regulatory B subunits (30). STs bind to the A and C subunit complexes (51, 64), displacing or preventing B subunits from binding. Since SVST binds to regions of the A subunit involved in B binding (12,14), the absence of B subunits in ST/PP2A complexes is not surprising.There is ample evidence suggesting that careful examination of ST is important. SVST contributes to the multioncoproteindirected transformation of human cells (24,59,76). Transgenic SVST contributes to mammary gland carcinogenesis (22). POLST complements MT for both transformation (4,45,49) and tumor induction (3). POLST effects on the cell cycle are well documented. POLST promotes cell cycle progression (46) and complements LT for S-phase induction (5, 51). Array analysis showed that SVST (43) and POLST (35) have large effects on cellular mRNA levels. SVST can transactivate (19,32,40,48,53,61,68) or repress (67) various promoters. POLST activates the fos (46) and myc (36) promoters. POLST is known to promote changes in viral chromatin structure that may underlie altered transcriptional activity (16). DNA viruses are very much concerned with issues of cell survival. It is therefore not surprising that both small Ts affect survival. Both POLST and SVST can be antiapoptotic. POLST can protect against serum starvation-induced apoptosis (2) and resists the effects of p53-induced apoptosis (54). SVST opposes apoptosis induced by LT (37) or CD95 (20). Both POLST (2) and SVST (21) can also be proapoptotic under some circumstances.Many ST functions are known to depend on their interactions with PP2A. Promotion of cell cycle by POLST (46), activation of promoters, such as myc (36), fos (4...

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“…The exact mechanism by which st-ag prevents apoptosis is not known, but may involve the prevention of PP2A-mediated dephosphorylation of Akt or its substrate Bax. Phosphorylation of Akt, a crucial event in PI3K/Akt-mediated cell survival, was increased in the livers of st-ag transgenic mice and in primary human keratinocytes expressing st-ag [114,119,120]. Phosphorylation levels of Bax, which is a pro-apoptotic protein, were also increased in SV40 stag-expressing cells [121].…”

Section: Effect On Apoptosis/cell Survivalmentioning

confidence: 97%

Oncogenic potentials of the human polyomavirus regulatory proteins

Moens

Ghelue

Johannessen

2007

Cell. Mol. Life Sci.

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The polyomaviruses BK, JC and SV40 are common in the human population. Their DNA genomes encode large T-antigen, small t-antigen, agnoprotein, and the capsid proteins VP1-3. Studies with these viruses have contributed extensively to the understanding of processes such as replication, transcriptional and posttranscriptional regulation, and cell cycle control. All three viruses can transform human cells in vitro, can induce tumours in animal models, and are strongly association with certain human cancers. It is generally assumed that large T-antigen is the major protein involved in neoplastic processes and that large T-antigen predominantly exerts its effect through deregulation of the tumour suppressors p53 and the retinoblastoma family members. However, additional properties of large T-antigen as well as the other viral proteins contribute to oncogenic processes. This review presents the different mechanisms by which the polyomavirus proteins can induce transformation and discusses which mechanisms may be operational in polyomavirus-positive cancers.

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Hepatic Expression of SV40 Small-t Antigen Blocks the in Vivo CD95-Mediated Apoptosis

Cited by 10 publications

References 46 publications

SV40-Dependent AKT Activity Drives Mesothelial Cell Transformation after Asbestos Exposure

SV40-Dependent AKT Activity Drives Mesothelial Cell Transformation after Asbestos Exposure

Comparisons between Murine Polyomavirus and Simian Virus 40 Show Significant Differences in Small T Antigen Function

Oncogenic potentials of the human polyomavirus regulatory proteins

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