Stimulation of p300-mediated Transcription by the Kinase MEKK1

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摘要：

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.

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关键词：

DNA-Binding Protein, Cyclic AMP-Responsive Nuclear Proteins Protein-Serine-Threonine Kinases DNA结合蛋白质, 环AMP反应性核蛋白质类蛋白质丝氨酸苏氨酸激酶反式作用因子

DOI：

10.1074/jbc.M008113200

被引量：

169

年份：

2001