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.