The adenovirus type 5 E1B-55K oncoprotein is a highly active shuttle protein and shuttling is independent of E4orf6, p53 and Mdm2

The E1B-55K and E4orf6 oncoproteins of adenovirus type 5 are involved in th e export of viral mRNAs, Previously, it cr as suggested that a complex comp osed of E1B-55K and E4orf6 serves as a nucleocytoplasmic transporter for vi ral mRNAs in which the E4orf6 protein directs both nuclear import and expor t, We now demonstrate that the E1B-55K protein itself shuttles efficiently in the absence of E4orf6, In addition, E1B-55K trafficking was independent of the defined shuttle proteins Mdm2 or p53, which interacts with E1B-55K, The identified N-terminal E1B-55K leucine-rich nuclear-export signal (NES) conferred rapid nuclear export even in a heterologous system in contrast to the postulated E4orf6NES, Interestingly, although shuttling was blocked by inhibitors of the CRM1 mediated export pathway, E1B-55K inhibited neither the activity nor the trafficking of the retroviral shuttle proteins HIV-1 R ev and HTLV-1 Rex, In contrast, Rev or Rex blocked the nuclear export of E1 B-55K, most likely by competing for essential export factors, Our results p rovide new insights into the regulation of the adenovirus mRNA export syste m and the processes of adenovirus mediated transformation.