Stimulation of p300-mediated transcription by the kinase MEKK1

p300 and CREB-binding protein (CBP) are related transcriptional coactivator s that possess histone acetyltransferase activity. Inactivation of p300/CBP is part of the mechanism by which adenovirus E1A induces oncogenic transfo rmation of cells. Recently, the importance of p300/CBP has been demonstrate d directly in several organisms including mouse, Drosophila, and Caenorhabd itis elegans where p300/CBP play an indispensable role in differentiation, in patterning, and in cell fate determination and proliferation during deve lopment. CBP/p300s are modified by phosphorylation during F9 cell different iation as well as adenovirus infection, suggesting that phosphorylation may play a role in the regulation of p300/CBP activity. Here we show that the mitogen-activated/extracellular response kinase kinase 1 (MEKK1) enhances p 300-mediated transcription. We identify several domains within p300 that ca n respond to MEKK1-induced transcriptional activation. Interestingly, activ ation of p300-mediated transcription by MEKK1 does not appear to require th e downstream kinase JNK and may involve either a direct phosphorylation of p300 by MEKK1 or by other non-JNK MEKK1-directed downstream kinases, Finall y, we present evidence that p300 is important for MEKK1 to induce apoptosis . Taken together, these results identify MEKK1 as a kinase that is likely t o be involved in the regulation of the transactivation potential of p300 an d support a role of p300 in MEKK1-induced apoptosis.