Disease relevance of MPyVgp2

• Middle T antigen as primary inducer of full expression of the phenotype of transformation by polyoma virus [1].
• Mice were immunized with small T antigen and a truncated mutant of middle T antigen, both purified from genetically engineered Escherichia coli [2].
• In polyoma virus the middle T antigen plays a role in virion maturation by influencing the phosphorylation of capsid proteins [3].

High impact information on MPyVgp2

• In order to investigate viral oncogenesis, we generated transgenic mice carrying either the Py large T antigen (LT) gene or the Py middle T antigen (MT) gene linked to Py early region regulatory sequences [4].
• Polyoma middle-T antigen is required for viral transformation of cultured cells and for tumorigenesis in animals [5].
• A subfraction of middle T antigen is associated with a protein kinase activity which phosphorylates middle T antigen in vitro on tyrosine [6].
• Middle T antigen is a major transforming protein which is responsible for the induction of the phenotype of transformed cells and, without it, transformation does not occur (reviewed in refs 1-4) [6].
• The viral middle T-antigen was found in association with most cytoplasmic membranes and in the majority of cells mainly in the endoplasmic reticulum [7].

Chemical compound and disease context of MPyVgp2

• Middle T antigen of polyoma virus has an associated tyrosine kinase activity which phosphorylates tyrosine residue 315 on middle T in immunoprecipitates [8].
• Antibodies were raised against the sequence Glu-Glu-Glu-Glu-Tyr-Met-Pro-Met -Glu, which represents a part of the middle T antigen of polyomavirus that is considered to be important in inducing the phenotype of transformed cells [9].

Biological context of MPyVgp2

• The results also provide the evidence that the carboxy-terminal region of middle T antigen and a part of large T antigen are encoded in the genome in the same DNA segment around map units 88 to 94 in different reading frames [1].
• In these cells, the low efficiency of dl1041 DNA replication could be attributed to deficiencies in both large and middle T-antigen, suggesting a link between the mitogenic and oncogenic activities of these proteins [10].
• Deletions of polyoma virus DNA around the region that codes for the C-terminus of the viral middle T-antigen were created using a transforming fragment (BamH I/EcoR I) of viral DNA cloned in the plasmid vector pAT153 [11].
• The transformation properties, as measured by colony formation in soft agar, of mutants with overlapping or contiguous deletions showed that part or all of the middle T antigen segment, consisting of the short amino acid sequence Glu4-Tyr-Met-Pro-Met, was essential for the activity of the protein in transformation [12].
• Early mutants of polyoma virus (dl8 and dl23) with altered transformation properties: is polyoma virus middle T antigen a transforming gene product [13]?

Anatomical context of MPyVgp2

• However, the small-T-antigen gene dramatically increased the rate of growth of NIH 3T3 cells transformed by middle T antigen in semisolid medium [14].
• We examined whether small T antigen would cooperate with middle T antigen in the in vitro transformation of NIH 3T3 (fibroblasts) and NRK-52E (epitheliallike) cells [14].
• Our study describes a novel murine model of MTC and provides evidence that the N-terminal 304 amino acid fragment of Py middle-T antigen, possibly in co-operation with small-T antigen, acts as a potent oncogene in c-cells of the thyroid [15].
• Middle T antigen alone can transform established cell lines, although large, and possibly small, T antigens are also required for the full expression of the phenotype of transformed cells in media with a low concentration of serum [6].

Associations of MPyVgp2 with chemical compounds

• These cells did not show anchorage-independent growth, despite the fact that middle-T-antigen-associated tyrosine protein kinase activity was clearly detected in these cells [14].
• Other methionine peptides were found only in the large or middle T-antigen forms [16].
• These proteins had approximate molecular weights of 105,000 (large T antigen), 63,000 (middle T antigen), and 20,000 (small T antigen) as estimated by acrylamide gel electrophoresis [16].
• These results indicate that this proline-rich domain in middle T antigen is important for oncogenesis in a wide variety of tissues and cell types [17].
• Antibody to the nonapeptide Glu-Glu-Glu-Glu-Tyr-Met-Pro-Met-Glu is specific for polyoma middle T antigen and inhibits in vitro kinase activity [8].

Other interactions of MPyVgp2

• Correlation with protein data suggests that one frame codes for part of middle T antigen and the other for part of large T antigen [18].

Analytical, diagnostic and therapeutic context of MPyVgp2

• Transforming activity of polyoma virus middle-T antigen probed by site-directed mutagenesis [19].
• This virus has been noted for its capacity to induce readily detected tumor-specific transplantation antigen in hamster cells, a property that is most likely attributable to an altered middle T-antigen [20].
• Immunoprecipitation of middle T antigen as well as 130K and 33K proteins was blocked by the peptide [9].

References