E1B 55-KILODALTON-ASSOCIATED PROTEIN - A CELLULAR PROTEIN WITH RNA-BINDING ACTIVITY IMPLICATED IN NUCLEOCYTOPLASMIC TRANSPORT OF ADENOVIRUSAND CELLULAR MESSENGER-RNAS

The adenovirus type 5 (Ad5) early 1B 55-kDa protein (E1B-55kDa) is a m ultifunctional phosphoprotein that regulates viral DNA replication and nucleocytoplasmic RNA transport in lytically infected cells. In addit ion, E1B-55kDa provides functions required for complete oncogenic tran sformation of rodent cells in cooperation with the E1A proteins. Using the far-Western technique, we have isolated human genes encoding E1B- 55kDa-associated proteins (E1B-APs). The E1B-AP5 gene encodes a novel nuclear RNA-binding protein of the heterogeneous nuclear ribonucleopro tein (hnRNP) family that is highly related to hnRNP-U/SAF-A. Immunopre cipitation experiments indicate that two distinct segments in the 55-k Da polypeptide which partly overlap regions responsible for p53 bindin g are required for complex formation with E1B-AP5 in Ad-infected cells and that this protein interaction is modulated by the adenovirus E4or f6 protein. Expression of E1B-AP5 efficiently interferes with Ad5 E1A/ E1B-mediated transformation of primary rat cells. Furthermore, stable expression of E1B-AP5 in Ad-infected cells overcomes the E1B-dependent inhibition of cytoplasmic host mRNA accumulation. These data suggest that E1B-AP5 might play a role in RNA transport and that this function is modulated by E1B-55kDa in Ad-infected cells.