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.
Jayaraman
G
G
Lurie Cancer Center and Microbiology and Immunology Department, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Srinivas
R
R
Duggan
C
C
Ferreira
E
E
Swaminathan
S
S
Somasundaram
K
K
Williams
J
J
Hauser
C
C
Kurkinen
M
M
Dhar
R
R
Weitzman
S
S
Buttice
G
G
Thimmapaya
B
B
D001665:Binding Sites; D050882:CREB-Binding Protein; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D051548:Histone Acetyltransferases; D006801:Humans; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D056921:Nuclear Receptor Coactivator 3; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D000071230:Transcriptional Regulator ERG
D004268:DNA-Binding Proteins; C107465:ERF protein, human; C072312:ERG protein, human; C494041:ETS1 protein, human; C494069:ETS2 protein, human; D009687:Nuclear Proteins; D050784:Proto-Oncogene Protein c-ets-1; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000071230:Transcriptional Regulator ERG; C065788:transcription factor PEA3; D050882:CREB-Binding Protein; C494363:CREBBP protein, human; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D019278:Matrix Metalloproteinase 3