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Mol Cell Biol, April 1998, p. 2218-2229, Vol. 18, No. 4
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

A Role for CREB Binding Protein and p300 Transcriptional Coactivators in Ets-1 Transactivation Functions

Cheng Yang,1 Linda H. Shapiro,2 Morris Rivera,1 Alok Kumar,2 and Paul K. Brindle1,*

Department of Biochemistry1 and Department of Experimental Oncology,2 St. Jude Children's Research Hospital, Memphis, Tennessee 38105

Received 21 November 1997/Returned for modification 30 December 1997/Accepted 19 January 1998

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.

* Corresponding author. Mailing address: Department of Biochemistry, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN, 38105. Phone: (901) 495-2522. Fax: (901) 525-8025. E-mail: paul.brindle{at}stjude.org.




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