Disease relevance of SV40gp7

• Soluble, monomeric simian virus 40 (SV40) small-t antigen (small-t) was purified from bacteria and assayed for its ability to form complexes with protein phosphatase 2A (PP2A) and to modify its catalytic activity [1].
• We report here for the first time, that the SV40 small t-antigen inhibits mammary gland differentiation during mid-pregnancy and that about 10% of multiparous WAP-SVt transgenic animals develop breast tumors with latencies ranging from 10-17 months [2].
• Simian virus 40 large T-antigen, but not small T-antigen, trans-activates the human cytomegalovirus major immediate early promoter [3].
• A murine recombinant Neo(r) retrovirus encoding the SV40 small t antigen was used to infect Balb/c 3T3 CIA31 cells [4].
• However, small intestinal neoplasms were extremely rare in the absence of small t antigen expression [5].

High impact information on SV40gp7

• Depleting Menin immortalizes primary human fibroblasts and causes a transformation phenotype when coupled with expression of SV40 Large and Small T antigen and oncogenic ras [6].
• A biochemical role for SV40 small t antigen (t) in the viral infectious cycle that would explain the strong conservation of t structure among papovaviruses and its role as a helper of SV40 large T antigen function in the viral transforming process is not understood [7].
• METHODS: Two SV40 early-region transgenes containing a deletion that eliminated expression of the small t antigen were expressed in transgenic mice under control of the secretin gene [5].
• The SV40 small T-antigen, which is similar to PyST in containing a J domain and in binding to the PP2A AC dimer, does not activate the MAP kinase cascade, but does stimulate phosphorylation of AKT in a PP2A-dependent manner [8].
• Interestingly, the polyoma small T-antigen (PyST), which shares with MTA both partial amino acid sequence homology and cellular location, also activates the MAP kinase cascade [8].

Chemical compound and disease context of SV40gp7

• The polyomavirus small T-antigen gene, together with the polyomavirus promoter, was inserted into a retrovirus vector pGV16 which contains the Moloney sarcoma virus long terminal repeat and neomycin resistance gene driven by the simian virus 40 promoter [9].
• A specific nuclear accumulation of greater than 20-fold is observed for the transformation-related nuclear proteins, p53 and E1b, and the nuclear enzyme, thymidine kinase, whereas transport of the nonnuclear proteins, dihydrofolate reductase and simian virus 40 small t antigen, is negligible within 30 min [10].
• Reversal of simian virus 40 small-t-antigen-induced theophylline resistance [11].
• The simian virus 40 small-t antigen contains 10 cysteine residues, 6 of which are organized in two CysXCysXXCys clusters [12].
• Simian virus 40 small-t antigen-induced theophylline resistance is not mediated by cyclic AMP [13].

Biological context of SV40gp7

• This mutant, which we term E107KDelta, has a deletion that eliminates synthesis of small t antigen and a point mutation (E107K) that results in loss of the ability to bind to Rb family members [14].
• Nucleotide sequence analysis of viable deletion mutants lacking segments of the simian virus 40 genome coding for small t antigen [15].
• Nucleotide sequence deletions within the coding region for small-t antigen of simian virus 40 [16].
• Markers of endothelium have been studied in a new endothelial cell line derived from human umbilical cord vein cells by microinjection of a recombinant gene that includes a deletion mutant of the human vimentin gene regulatory region controlling the large T and small t antigen coding region of the SV40 virus [17].
• Transient transfection studies in A549 cells demonstrated that SV40 large T-antigen, but not small t-antigen, trans-activated MIEP activity approximately 9-fold [3].

Anatomical context of SV40gp7

• Cyclin D1 is deregulated and over expressed in the small t-antigen positive mammary gland epithelial cells (ME-cells) and in the breast tumor cells [2].
• We observed that continuous and rapid division of myoblasts occurs at permissive temperature, suggesting that immortalization is achieved even though the small t antigen is absent [18].
• The SV40 small t antigen is essential for the morphological transformation of human fibroblasts [19].
• The stable expression of small T antigen is noted particularly because cell lines expressing small T antigen have not been readily available prior to the use of retroviral vectors [20].
• Small T antigen-induced increase in saturation density of NIH 3T3 cells can be scored on the basis of the morphology of drug-resistant colonies [20].

Associations of SV40gp7 with chemical compounds

• The small-t-antigen-induced increase in Akt and PKC lambda activities was not inhibited by wortmannin, while the ability of small t antigen to enhance glucose transport was inhibited by dominant negative Akt (DN-Akt) expression and Akt small interfering RNA (siRNA) but not by DN-PKC lambda expression or PKC lambda siRNA [21].
• Furthermore, Shc tyrosine phosphorylation and its association with Grb2 were also elevated in small-t-antigen-expressing cells [22].
• Elevated levels of cyclic AMP are not involved in growth arrest of CV-1 cells by methylxanthines, and small-t antigen does not alter cyclic AMP levels dramatically after infection [13].
• In the presence of N-ethylmaleimide, the 37-kDA protein was selectively released from immune complexes, leaving the small-t antigen and 61-kDa protein in association [23].
• As observed with 10 nM OA, both phospho-ser15-p53 levels and p53 activity were increased by 10 microM fostriecin or SV40 small t-antigen [24].

Regulatory relationships of SV40gp7

• SV40 small t antigen enhances the transformation activity of limiting concentrations of SV40 large T antigen [4].

Analytical, diagnostic and therapeutic context of SV40gp7

• Of the 15 G418-resistant cell clones, 8 express small T antigen at various levels as revealed by immunoprecipitation [9].
• Oligonucleotide-directed mutagenesis was used to generate a series of deletion and substitution mutants within the amino-terminal 82 residues of T, the segment which is shared with simian virus 40 small t antigen (t) [25].
• In summary, the LPB-Tag animal model is unique in that it is the only model generated with the Tag alone, thereby eliminating any influences of the small t antigen on prostate tumor formation [26].
• The regions of the SV40 genome targeted by PCR include the large T-antigen, the small t-antigen, the origin of replication, and viral protein-1 capsid protein [27].
• Simian virus 40 small T-antigen splice and polyadenylation signals were included to produce a mature transcript coding for t-PA, whose activity can be detected in single cells by a fibrin-agarose plaque assay [28].

References