Adenovirus E4orf4 protein binds to protein phosphatase 2A, and the complex down regulates E1A-enhanced junB transcription.

Adenovirus E4orf4 protein was previously shown to counteract transactivation of junB by cyclic AMP (cAMP) and E1A protein. It was also shown to cause hypophosphorylation of E1A and c-Fos proteins. Here we show that the E4orf4 protein associates with protein phosphatase 2A. All three subunits of the phosphatase are present in the complex, and the B subunit interacts directly with the viral protein. The complex possesses a phosphatase activity typical of protein phosphatase 2A, and the phosphatase mediates the E4orf4-induced down regulation of junB transcription. Thus, adenovirus E4orf4 protein recruits protein phosphatase 2A into a signal transduction pathway initiated by cAMP and E1A protein.