p202, an interferon-inducible negative regulator of cell growth, is a target of the adenovirus E1A protein

Studies have revealed that human adenovirus-encoded E1A protein promotes ce ll proliferation through the targeted interaction with cellular proteins th at act as key negative regulators of cell growth. The targets of E1A protei n include the retinoblastoma tumor suppressor protein (pRb). Because p202, an interferon (IFN)inducible murine protein (52-kDa), negatively regulates cell growth in part through the pRb/E2F pathway, we tested whether the p202 is a target of the adenovirus-encoded E1A protein for functional inactivat ion. Here we report that the expression of E1A protein overcame p202-mediat ed inhibition of cell growth and this correlated with an alleviation of p20 2-mediated inhibition of the transcriptional activity of E2F. Furthermore, E1A protein relieved p202-mediated inhibition of the specific DNA-binding a ctivity of E2F complexes, including those containing the pocket proteins. A dditionally, the E1A protein bound to p202 both in vitro and in vivo and a deletion of four amino acids in the conserved region 2 (CR2) of E1A protein significantly reduced the binding of E1A to p202. Interestingly, ectopic e xpression of p202 under reduced serum conditions significantly reduced E1A- mediated apoptosis. Taken together, our observations provide support to the idea that the p202 and adenovirus E1A protein functionally counteract each other and E1A protein targets p202 to promote cell proliferation.