Adenovirus E1A-p105 (Rb) protein interactions play a direct role in the initiation but not the maintenance of the rodent cell transformed phenotype
Nielsch, U.; Fognani, C.; Babiss, L.E.
Oncogene 6(6): 1031-1036
1991
ISSN/ISBN: 0950-9232 PMID: 2067843 Document Number: 375818
The morphological transformation of rodent fibroblast cells by adenovirus requires expression of the viral E1A and E1B genes. Recent studies have suggested that one function of the E1A proteins is to interact with and inactivate specific cellular proteins (anti-oncoproteins) that maintain regulated cell growth. One candidate cellular protein that may be influenced by its interaction with the E1A oncoproteins is the retinoblastoma (Rb) susceptibility gene product. In this report we show that over-expression the human Rb protein in two rodent fibroblast cell lines leads to a significant reduction in the frequency of focus-formation following adenovirus infection. Therefore, Rb-E1A protein interactions play an important role in the initiation of cellular transformation by adenovirus. Using cell lines which are conditionally transformed by adenovirus mutants which fail to express the E1A 289R protein, we show that the process leading to a loss of the maintenance of the transformed cell phenotype is not associated with changes in the levels of E1A-Rb protein complexes. These observations suggest distinct roles of Rb-E1A interactions in initiating and maintaining the transformed cell phenotype. Finally, in contrast to results with the SV40 large T Ag, we find that E1A protein expression has no affect on cellular Rb gene expression in both virus-infected and virus-transformed cell lines.