p300/cAMP-responsive element-binding protein interactions with ets-1 and ets-2 in the transcriptional activation of the human stromelysin promoter.

In this paper we show that transcription factors Ets-1 and Ets-2 recruit transcription adapter proteins p300 and CBP (cAMP-responsive element-binding protein) during the transcriptional activation of the human stromelysin promoter, which contains palindromic Ets-binding sites. Ets-2 and p300/CBP exist as a complex in vivo. Two regions of p300/CBP between amino ...
acids (a.a.) 328 and 596 and a. a. 1678 and 2370 independently can interact with Ets-1 and Ets-2 in vitro and in vivo. Both these regions of p300/CBP bind to the transactivation domain of Ets-2, whereas the C-terminal region binds only to the DNA binding domain of Ets-2. The N- and the C-terminal regions of CBP (a.a. 1-1097 and 1678-2442, respectively) which lack histone acetylation activity independently are capable of coactivating Ets-2. Other Ets family transcription factors failed to cooperate with p300/CBP in stimulating the stromelysin promoter. The LXXLL sequence, reported to be important in receptor-coactivator interactions, does not appear to play a role in the interaction of Ets-2 with p300/CBP. Previous studies have shown that the stimulation of transcriptional activation activity of Ets-2 requires phosphorylation of threonine 72 by the Ras/mitogen-activated protein kinase signaling pathway. We show that mutation of this site does not affect its capacity to bind to and to cooperate with p300/CBP.
Mesh Terms:
Binding Sites, CREB-Binding Protein, Calcium-Calmodulin-Dependent Protein Kinases, DNA-Binding Proteins, Histone Acetyltransferases, Humans, Matrix Metalloproteinase 3, Mutation, Nuclear Proteins, Nuclear Receptor Coactivator 3, Precipitin Tests, Promoter Regions, Genetic, Protein Binding, Proto-Oncogene Protein c-ets-1, Proto-Oncogene Protein c-ets-2, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-ets, Repressor Proteins, Trans-Activators, Transcription Factors, Transcriptional Activation
J. Biol. Chem.
Date: Jun. 11, 1999
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