Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Binding Sites
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CREB-Binding Protein
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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DNA-Binding Proteins / metabolism
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Histone Acetyltransferases
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Humans
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Matrix Metalloproteinase 3 / biosynthesis*
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Matrix Metalloproteinase 3 / genetics
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Mutation
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Nuclear Proteins / metabolism*
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Nuclear Receptor Coactivator 3
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Precipitin Tests
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Promoter Regions, Genetic
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Protein Binding
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Proto-Oncogene Protein c-ets-1
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Proto-Oncogene Protein c-ets-2
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-ets
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Repressor Proteins*
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / metabolism*
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Transcriptional Activation*
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Transcriptional Regulator ERG
Substances
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DNA-Binding Proteins
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ERF protein, human
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ERG protein, human
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ETS1 protein, human
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ETS2 protein, human
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Nuclear Proteins
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Proto-Oncogene Protein c-ets-1
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Proto-Oncogene Protein c-ets-2
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-ets
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Repressor Proteins
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Trans-Activators
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Transcription Factors
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Transcriptional Regulator ERG
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transcription factor PEA3
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CREB-Binding Protein
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CREBBP protein, human
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Histone Acetyltransferases
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NCOA3 protein, human
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Nuclear Receptor Coactivator 3
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Calcium-Calmodulin-Dependent Protein Kinases
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Matrix Metalloproteinase 3