Two independent activation domains in c-Ets-1 and c-Ets-2 located in non-conserved sequences of the ets gene family.
The c-Ets-1 oncoprotein is a transcription activator that specifically binds to DNA. We show, using fusion proteins with heterologous DNA-binding domains, that chicken c-Ets-1 (p68) contains two independent activation domains. The N-terminal activation domain is absent in c-Ets-1 (p54) that is generated from an alternatively spliced mRNA. A closely related member of the ets gene family, c-Ets-2, also contains two separate activation domains. They lie in the regions of the protein that are least conserved with c-Ets-1, suggesting that the activating function will determine the different physiological roles of these two proteins. The activation domains of c-Ets-1 (p68) and -2 are separated by a moderately conserved region that does not activate on its own. These sequences appear to affect stimulation by the domains, suggesting that they regulate transcription activation. Competition experiments show that c-Ets-1 and -2 interact with a common limiting coactivator. These studies provide important clues about the physiological roles of closely related members of the ets gene family.
Schneikert
J
J
CNRS-LGME/INSERM-U. 184, Institut de Chimie Biologique, Faculté de Médecine, Strasbourg, France.
Lutz
Y
Y
Wasylyk
B
B
D000818:Animals; D001665:Binding Sites; D002451:Cell Compartmentation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000737:chemistry*; D066298:In Vitro Techniques; D051379:Mice; D008970:Molecular Weight; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012097:Repressor Proteins; D013329:Structure-Activity Relationship; D015534:Trans-Activators; D014157:Transcription Factors / Q000737:chemistry*
D004268:DNA-Binding Proteins; C107465:ERF protein, human; C494070:Ets2 protein, mouse; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors