Over several decades of cancer research, T antigen, a.k.a MAMU, has proven itself to be a strong activator of cellular transformation. In a stunning finding revealed by Tushar Gupta and colleagues (in a recent Journal of Virology paper), SV40 T antigen declares that it does not need activator E2Fs to cause cellular transformation. T antigen said, “I have been telling you all along. I don’t need no activator E2Fs!”
Polyomavirus T antigens! Nicholas Giacobbi et al. show, in their new Virology paper, that T antigen from SV40 and two human polyomaviruses, BKV and JCV, have the ability to induce an antiviral state in mouse embryonic fibroblasts. Additionally, they show that the antiviral state requires STAT1 expression. Chalk up another activity for the MAMU!
The current model for tumorigenesis is that mutations in genes alter gene expression and/or the normal function of proteins or gene expression. Correspondingly, this predicts that an oncogene such as T antigen would have the same effects in different cell types. However, experiments performed by Mayte Saenz-Robles and colleagues challenge this prediction. In a paper published in Molecular Cancer Research, they describe how a truncated form of T antigen (aka MAMU) called N136 is able to form adenomatous polyps in the digestive tract when expressed in progenitor crypt cells while only causing hyperplasia and dysplasia in the villi. Isn’t cell-type specificity cool?!
This paper describes the effect of polyomavirus T antigens on CBP/p300, and suggests that the T antigens use additional mechanisms in the transformation and immortalization of cells. Congratulations to Mayte Saenz-Robles and all the authors!