Mammalian Srb Mediator complex is targeted by adenovirus E1A protein

Adenovirus E1A proteins prepare the host cell for viral replication, stimul ating cell cycling and viral transcription through interactions with critic al cellular regulatory proteins such as RB1,2 and CBP3. Here we show that t he E1A zinc-finger domain that is required to activate transcription of vir al early genes binds to a host-cell multiprotein complex containing homolog ues of yeast Srb/Mediator proteins(4,5). This occurs through a stable inter action with the human homologue of Caenorhabditis elegans SUR-2, a protein required for many developmental processes in the nematode(6). This human Sr b/Mediator complex stimulates transcription in vitro in response to both th e E1A zinc-finger and the herpes simplex virus VP16 activation domains. Int eraction with human Sur-2 is also required for transcription to be activate d by the activation domain of a transcription factor of the ETS-family in r esponse to activated mitogen-activated protein (MAP) kinase.