CLONING AND CHARACTERIZATION OF ERF-1, A HUMAN MEMBER OF THE TIS11 FAMILY OF EARLY-RESPONSE GENES

Members of the Tis11 family of early-response genes are characterized by a high degree of sequence similarity around a putative zinc finger motif. They are induced by a variety of cell agonists and polypeptide mitogens, including 12-O-tetradecanoylphorbol-13-acetate (TPA) and epi dermal growth factor (EGF). We describe the cloning and sequencing of a human member of this gene family, EGF-response factor 1 (ERF-1), the homolog of the mouse Tis11b/rat cMG1 genes. The human and rodent gene s are similar, with 5' UTR, coding sequence, and 3' UTR highly conserv ed. The promoter/enhancer region and intron sequences contain multiple putative transcription factor binding motifs characteristic of early- response genes. Amino acid sequence comparison of the seven members of the Tis11 family cloned so far identifies a repeated consensus motif of (x(+))YKTELC(x(+))x(5)GxCxYGx(x(+))CxFxH involving the potential zi nc finger. Toward the carboxy-terminal end is a region with a high per centage of prolines (15/73) and, partially overlapping, a serine-rich domain (20/54). These may be important as trans-activation and phospho rylation sites. The 3' untranslated region is unusually long, extendin g over 1,860 bp. The sequence immediately downstream from the translat ional stop codon has extensive secondary structure potential. The 3' U TR is 60% AT rich, but contains two GC rich (> 70%) regions. In additi on there are multiple reiterations of a destabilization sequence, as w ell as a single UUAUUUAU motif characteristic of mRNAs specifying prot eins involved in the inflammatory response. The mRNA contains a consen sus polyadenylation signal.