The ETS Family of Transcriptional Regulators

The identification of the v-ets oncogene of avian leukemia virus E26 (Leprince et al, 1983; Nunn et al, 1983) has set the stage for the definition of a large protein family of over 30 members characterized by the presence of a conserved domain of about 85 amino acids, the ETS domain (Figure 2.1). For several years and despite the molecular cloning of the cDNAs of several ETS family members including c-ets-1, the cellular homolog of v-ets (Duterque-Coquillaud et al, 1988; Watson et al, 1988 a; Leprince et al, 1988), c-ets-2 (Boulukos et al, 1988; Watson et al, 1988 a), erg (ets related gene) (Reddy et al, 1987) and elk (ets like gene) (Rao et al, 1989), the analysis of the deduced amino acid sequence of the corresponding proteins failed to give any clue as to the nature of their biochemical function. The description of ETS-1 as a nuclear, chromatin-associated protein endowed with general DNA binding activity (Pognonec et al, 1989) and the fact that these properties all depended upon the integrity of the ETS domain (E domain) (Boulukos et a1, 1989) were the first indications for a possible nuclear function for ETS proteins. Definitive experimental evidence supporting this view was provided by a series of independent observations which identified ETS-1 as a sequence-specific DNA binding protein and transcriptional activator of viral and cellular promoters (Bosselut et al, 1990; Gunther et al, 1990; Ho et al, 1990; Wasylyk et al, 1990) and the concomitant identification of the SV40 PU-box transcription factor as an ETS protein (Klemsz et al, 1990).