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

Gopalswamy Jayaraman, Rampalli Srinivas, Catherine Duggan, Elisabeth Ferreira, Sathyamangalam Swaminathan, Kumaravel Somasundaram, Justin Williams, Craig Hauser, Markku Kurkinen, Ravi Dhar, Sigmund Weitzman, Giovanna Buttice, Bayar Thimmapaya*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)17342-17352
Number of pages11
JournalJournal of Biological Chemistry
Volume274
Issue number24
DOIs
StatePublished - Jun 11 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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