Inhibition of Rb and p53 is insufficient for SV40 T-antigen transformation.
The SV40 large T-antigen (TAg) has proven useful in studying pathways involved with cell division and tissue homeostasis. TAg disrupts the normal action of tumor suppressors pRb and p53. It is unclear whether T-antigen inhibition of p53 and pRb is sufficient for oncogenic transformation or if additional T-antigen activities are required. To pursue this question, cell lines were generated that coexpress an amino-terminal fragment of T-antigen (TAgN136), which has been shown to be sufficient to block pRb function, together with a dominant-negative p53. Neither focus formation nor saturation density was enhanced by coexpression of the dominant-negative p53 molecule, p53DD, along with TAgN136. Furthermore, a full-length TAg mutant incapable of binding p53 was capable of relieving contact inhibition, a hallmark of transformation. These results suggest the presence of a novel transforming activity in addition to the binding and inactivation of p53, requiring TAg amino acids 137 to 708.
Sachsenmeier
K F
KF
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Pipas
J M
JM
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000502:physiology*; D003260:Contact Inhibition; D005455:Fluorescent Antibody Technique; D015151:Immunoblotting; D051379:Mice; D010957:Plasmids; D051381:Rats; D016160:Retinoblastoma Protein / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D000952:Antigens, Polyomavirus Transforming; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53