A role for CREB binding protein and p300 transcriptional coactivators in Ets-1 transactivation functions.
The Ets-1 transcription factor plays a critical role in cell growth and development, but the means by which it activates transcription are still unclear (J. C. Bories, D. M. Willerford, D. Grevin, L. Davidson, A. Camus, P. Martin, D. Stehelin, F. W. Alt, and J. C. Borles, Nature 377:635-638, 1995; N. Muthusamy, K. Barton, and J. M. Leiden, Nature 377:639-642, 1995). Here we show that Ets-1 binds the transcriptional coactivators CREB binding protein (CBP) and the related p300 protein (together referred to as CBP/p300) and that this interaction is required for specific Ets-1 transactivation functions. The Ets-1- and c-Myb-dependent aminopeptidase N (CD13/APN) promoter and an Ets-1-dependent artificial promoter were repressed by adenovirus E1A, a CBP/p300-specific inhibitor. Furthermore, Ets-1 activity was potentiated by CBP and p300 overexpression. The transactivation function of Ets-1 correlated with its ability to bind an N-terminal cysteine- and histidine-rich region spanning CBP residues 313 to 452. Ets-1 also bound a second cysteine- and histidine-rich region of CBP, between residues 1449 and 1892. Both Ets-1 and CBP/p300 formed a stable immunoprecipitable nuclear complex, independent of DNA binding. This Ets-1-CBP/p300 immunocomplex possessed histone acetyltransferase activity, consistent with previous findings that CBP/p300 is associated with such enzyme activity. Our results indicate that CBP/p300 may mediate antagonistic and synergistic interactions between Ets-1 and other transcription factors that use CBP/p300 as a coactivator, including c-Myb and AP-1.
Yang
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Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Shapiro
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Rivera
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Kumar
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Brindle
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D000123:Acetyltransferases / Q000378:metabolism; D018826:CD13 Antigens / Q000235:genetics; D050882:CREB-Binding Protein; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D051548:Histone Acetyltransferases; D006801:Humans; D019169:Jurkat Cells; D009687:Nuclear Proteins / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D050783:Proto-Oncogene Proteins c-ets; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation
C494041:ETS1 protein, human; D009687:Nuclear Proteins; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA; D000123:Acetyltransferases; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051548:Histone Acetyltransferases; D018826:CD13 Antigens