THE X-PROTEIN OF HEPATITIS-B VIRUS COACTIVATES POTENT ACTIVATION DOMAINS

Transactivation by hepatitis B virus X protein (pX) is promiscuous, bu t it requires cellular activators. To study the mode of action of pX, we coexpressed pX with Gal4-derived activators in a cotransfection sys tem. Twelve different activators bearing different types of activation domains were compared for their response to pX. Because pX indirectly increases the amount of the activators, tools were developed to compa re samples with equivalent amount of activators. We demonstrate that p X preferentially coactivates potent activators, especially those with acidic activation domains. Weak activators with nonacidic activation d omains are not potentiated by pX. Interestingly, Gal4E1a, which is not rich in acidic residues but interacts with similar molecular targets, also responds to pX. The response to pX correlated with the strength of the activation domain. Collectively, these data imply that pX is a coactivator, which offers a molecular basis for the pleiotropic effect s of pX on transcription.