The t-unique coding domain is important to the transformation maintenance function of the simian virus 40 small t antigen.

Bikel, Ilan; Mamon, Harvey J.; Brown, Eric L.; Boltax, Jay; Agha, Mounzer; Livingston, David M.

doi:10.1128/mcb.6.4.1172

Cited by 35 publications

(22 citation statements)

References 39 publications

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“…Because others have observed that expression of small t Previous work has demonstrated that expression of SV40 large T is sufficient to transform cycling but not resting cells (5,6,8,11,14,19,36,37,41,45,46). Transformation can occur in resting cells, however, if either small t is coexpressed or the cells are treated with phorbol esters.…”

Section: Resultsmentioning

confidence: 99%

Simian virus 40 small t antigen cooperates with mitogen-activated kinases to stimulate AP-1 activity.

et al. 1994

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The simian virus 40 small tumor antigen (small t) specifically interacts with protein phosphatase type 2A (PP2A) in vivo and alters its catalytic activity in vitro. Among the substrates for PP2A in vitro are the activated forms of MEK and ERK kinases. Dephosphorylation of the activating phosphorylation sites on MEK and ERKs by PP2A in vitro results in a decrease in their respective kinase activities. Recently, it has been shown that overexpression of small t in CV-1 cells results in an inhibition of PP2A activity toward MEK and ERK2 and a constitutive upregulation of MEK and ERK2 activity. Previously, we have observed that overexpression of either ERK1, MEK1, or a constitutively active truncated form of c-Raf-1 (BXB) is insufficient to activate AP-1 in REF52 fibroblasts. We therefore examined whether overexpression of small t either alone or in conjunction with ERK1, MEK1, or BXB could activate AP-1. We found that coexpression of small t and either ERK1, MEKI, or BXB resulted in an increase in AP-1 activity, whereas expression of either small t or any of the kinases alone did not have any effect. Similarly, coexpression of small t and ERK1 activated serum response element-regulated promoters. Coexpression of kinase-deficient mutants of ERK1 and ERK2 inhibited the activation of AP-1 caused by expression of small t and either MEK1 or BXB. Coexpression of an interfering MEK, which inhibited AP-1 activation by small t and BXB, did not inhibit the activation of AP-1 caused by small t and ERK1. In contrast to REF52 cells, we observed that overexpression of either small t or ERK1 alone in CV-1 cells was sufficient to stimulate AP-1 activity and that this stimulation was not enhanced by expression of small t and ERK1 together. These results show that the effects of small t on immediate-early gene expression depend on the cell type examined and suggest that the mitogen-activated protein kinase activation pathway is distinctly regulated in different cell types.The stimulation of quiescent cells with growth factors induces widespread changes in gene expression, including the activation of promoters controlled by the transcription factor AP-1 (30). Following the binding of growth factors to cell surface receptors, a protein kinase cascade is activated, which generally results in the activation of two kinases termed ERK1 and ERK2. ERK1 and ERK2 belong to a family of kinases known as extracellular signal-regulated kinases (ERKs) or mitogen-activated protein (MAP) kinases (12). Both ERKI and ERK2 are activated by phosphorylation on specific threonine and tyrosine residues (44). This phosphorylation is catalyzed by a threonine/tyrosine kinase known as MEK (MAP and ERK kinase) (15,16,53,54,57). MEK itself is activated by phosphorylation on uncharacterized serine and/or threonine residues by both c-Raf-1 or MEK kinase (17,28,31,32,58 ing threonine in ERK1 and ERK2, and the activating serines and threonines in MEK1 (1,4,7,22,23,27,28,31). It is not entirely clear, however, how PP2A impacts this cascade in vivo. Indirect evidence s...

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Section: Resultsmentioning

confidence: 99%

Simian virus 40 small t antigen cooperates with mitogen-activated kinases to stimulate AP-1 activity.

et al. 1994

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“…ST cannot transform cells alone, although it may enhance the eciency with which transformation occurs (Bouck et al, 1978;Bikel et al, 1986;Fanning, 1992) and it can complement a LT mutant deleted for the N-terminal 82 amino acids (Montano et al, 1990). There is also evidence that 17kT can transform cells independently of LT (Zerrahn et al, 1993).…”

Section: Abstract: Sv40 T Antigens; Apoptosismentioning

confidence: 99%

Inhibition of SV40 large T antigen induced apoptosis by small T antigen

Kolzau

Hansen²,

Zahra

et al. 1999

Oncogene

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“…A portion of the T155 DNA sequence also encodes SV40 small t by an alternative splicing mechanism, and the two proteins have amino acid residues 1-82 in common (Jog et al, 1990;Paucha et al, 1978). Small t is believed to be critical for the transformation of cells but is not required for immortalization (Bikel et al, 1986(Bikel et al, ,1987Bouck et al, 1978;Fanning, 1992). While the functions of small t are incompletely understood, in cells that have been subjected to SV40 infection, it is reported to enhance viral replication and polyploidy of the host cells (Whalen et al, 1999) to facilitate transformation of the infected cells by LT in limiting growth conditions (Bikel et al, 1987;Martin and Chou, 1975;Rubin et al, 1982) and to promote induction of cell cycle progression in non-dividing cells, (Porras et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Truncated N-terminal mutants of SV40 large T antigen as minimal immortalizing agents for CNS cells

Freed

Zhang

Sanchez

et al. 2005

Experimental Neurology

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Immortalized central nervous system (CNS) cell lines are useful as in vitro models for innumerable purposes such as elucidating biochemical pathways, studies of effects of drugs, and ultimately, such cells may also be useful for neural transplantation. The SV40 large T (LT) oncoprotein, commonly used for immortalization, interacts with several cell cycle regulatory factors, including binding and inactivating p53 and retinoblastoma family cell-cycle regulators. In an attempt to define the minimal requirements of SV40 T antigen for immortalizing cells of CNS origin, we constructed T155c, encoding the N-terminal 155 amino acids of LT. The p53 binding region is known to reside in the C-terminal region of LT. An additional series of mutants was produced to further narrow the molecular targets for immortalization, and plasmid vectors were constructed for each. In a p53 temperature sensitive cell line model, T64-7B, expression of T155c and all constructs having mutations outside of the first 82 amino acids were capable of overriding cell-cycle block at the nonpermissive growth temperature. Several cell lines were produced from fetal rat mesencephalic and cerebral cortical cultures using the T155c construct. The E107K construct contained a mutation in the Rb binding region, but was nonetheless capable of overcoming cell cycle block in T64-7B cell and immortalizing primary cultured cells. Cells immortalized with T155c were often highly dependent on the presence of bFGF for growth. Telomerase activity, telomere length, growth rates, and integrity of the p53 gene in cells immortalized with T155c did not change over 100 population doublings in culture, indicating that cells immortalized with T155c were generally stable during long periods of continuous culture.

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The t-unique coding domain is important to the transformation maintenance function of the simian virus 40 small t antigen.

Cited by 35 publications

References 39 publications

Simian virus 40 small t antigen cooperates with mitogen-activated kinases to stimulate AP-1 activity.

Simian virus 40 small t antigen cooperates with mitogen-activated kinases to stimulate AP-1 activity.

Inhibition of SV40 large T antigen induced apoptosis by small T antigen

Truncated N-terminal mutants of SV40 large T antigen as minimal immortalizing agents for CNS cells

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