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Virology. 2001 Apr 25;283(1):40-8.

Inhibition of Rb and p53 is insufficient for SV40 T-antigen transformation.

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1
Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.

Abstract

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.

PMID:
11312660
DOI:
10.1006/viro.2001.0866
[Indexed for MEDLINE]
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