Stimulation of p300-mediated transcription by the kinase MEKK1.
p300 and CREB-binding protein (CBP) are related transcriptional coactivators that possess histone acetyltransferase activity. Inactivation of p300/CBP is part of the mechanism by which adenovirus E1A induces oncogenic transformation of cells. Recently, the importance of p300/CBP has been demonstrated directly in several organisms including mouse, Drosophila, and Caenorhabditis elegans where ... p300/CBP play an indispensable role in differentiation, in patterning, and in cell fate determination and proliferation during development. CBP/p300s are modified by phosphorylation during F9 cell differentiation 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 p300-mediated transcription. We identify several domains within p300 that can respond to MEKK1-induced transcriptional activation. Interestingly, activation of p300-mediated transcription by MEKK1 does not appear to require the downstream kinase JNK and may involve either a direct phosphorylation of p300 by MEKK1 or by other non-JNK MEKK1-directed downstream kinases. Finally, we present evidence that p300 is important for MEKK1 to induce apoptosis. Taken together, these results identify MEKK1 as a kinase that is likely to be involved in the regulation of the transactivation potential of p300 and support a role of p300 in MEKK1-induced apoptosis.
Mesh Terms:
Animals, Apoptosis, Caenorhabditis elegans, Cell Line, Cloning, Molecular, Cyclic AMP Response Element-Binding Protein, DNA-Binding Proteins, Drosophila, E1A-Associated p300 Protein, Fungal Proteins, Hela Cells, Humans, JNK Mitogen-Activated Protein Kinases, Kinetics, MAP Kinase Kinase Kinase 1, Mice, Mitogen-Activated Protein Kinases, Nocodazole, Nuclear Proteins, Phosphorylation, Protein-Serine-Threonine Kinases, Recombinant Proteins, Saccharomyces cerevisiae Proteins, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Cells, Cultured
Animals, Apoptosis, Caenorhabditis elegans, Cell Line, Cloning, Molecular, Cyclic AMP Response Element-Binding Protein, DNA-Binding Proteins, Drosophila, E1A-Associated p300 Protein, Fungal Proteins, Hela Cells, Humans, JNK Mitogen-Activated Protein Kinases, Kinetics, MAP Kinase Kinase Kinase 1, Mice, Mitogen-Activated Protein Kinases, Nocodazole, Nuclear Proteins, Phosphorylation, Protein-Serine-Threonine Kinases, Recombinant Proteins, Saccharomyces cerevisiae Proteins, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Cells, Cultured
J. Biol. Chem.
Date: May. 11, 2001
PubMed ID: 11278389
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