ABSTRACT
Transcription factors determine gene expression by binding to the specific DNA sequences within the promoter regions, by forming complexes with co-regulatory proteins, and by allowing transcriptional activation or repression. The ETS (E twenty-six) family of transcription factors is defined by a conserved DNA-binding ETS “domain” that binds to a purine-rich consensus core sequence GGA(A/T) of ETS binding motif in the promoter or enhancer region of target genes (for a review, see Wasylyk et al., 1993). ETS domain is composed of 85 amino acids and forms a winged helix-turn-helix structure with three α-helices and four fJ-sheets. At present, more than 50 proteins containing this ETS domain are identified in species ranging from drosophila to human, and they are divided into several subclasses according to the position of the ETS domain and the presence of specific subdomains. Most ETS family members activate gene transcription, while some such as ERF, NET, TEL and YAN act as transcriptional repressors (for a review, see Mavrothalassitis and Ghysdael, 2000). Regions beside the ETS domain also influence the function of the ETS family members. In at least seven ETS family members, two inhibitory regions flanking the ETS domain negatively regulate the binding to DNA. Especially, the N-terminal flanking region is responsible for inhibition of DNA binding by interacting with ETS domain and with the C-terminal flanking region. This inhibition is disrupted by the unfolding of an α-helix in ETS domain, which renders the binding of ETS domain to DNA. Pointed domain, which is homologous to a drosophila ETS family member Pointed, is also conserved in a number of ETS family members. Pointed domain contains target amino acid sequences for MAP kinase, and once these sequences are phosphorylated by MAP kinase, transactivation activity of ETS protein is markedly enhanced (for reviews, see Papas et al., 1997; Sharrocks, 2001).
