Cloning and Characterization of ERF-1, a Human Member of the Tis11 Family of Early-Response Genes

Abstract

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 epidermal 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 genes are similar, with 5' UTR, coding sequence, and 3' UTR highly conserved. 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+)x5GxCxYGx(x+)CxFxH involving the potential zinc finger. Toward the carboxyterminal end is a region with a high percentage of prolines (15/73) and, partially overlapping, a serine-rich domain (20/54). These may be important as trans-activation and phosphorylation sites. The 3' untranslated region is unusually long, extending over 1,860 bp. The sequence immediately downstream from the translational stop codon has extensive secondary structure potential. The 3' UTR is 60% AT rich, but contains two GC rich (> 70%) regions. In addition there are multiple reiterations of a destabilization sequence, as well as a single UUAUUUAU motif characteristic of mRNAs specifying proteins involved in the inflammatory response. The mRNA contains a consensus polyadenylation signal.

The RNA binding protein Zfp36l1 is required for normal vascularisation and post‐transcriptionally regulates VEGF expression

“…Zfp36l1 (also called TIS11b, BRF-1, Berg36, cMG1, ERF-1) (Gomperts et al, 1990;Varnum et al, 1991;Barnard et al, 1993;Bustin et al, 1994;Maclean et al, 1995;Ning et al, 1996) belongs to a family of mRNA-binding proteins possessing an unusual and highly conserved zinc finger motif, comprising a tandem YKTEL CX 8 CX 5 CX 3 H sequence, spaced exactly 18 amino acids apart. The prototype of this family, tristetraprolin (TTP, Tis11, Nup475, G0S24) (Varnum et al, 1989;DuBois et al, 1990;Lai et al, 1990;Ma and Herschman, 1991;Heximer and Forsdyke, 1993) is the product of an immediate early response gene Zfp36 in the mouse.…”

A Unique C-terminal Repeat Domain Maintains the Cytosolic Localization of the Placenta-specific Tristetraprolin Family Member ZFP36L3

“…The mammalian members of the tristetraprolin (TTP) 2 family of CCCH tandem zinc finger (TZF) proteins include TTP (also known as ZFP36) (1-6), ZFP36L1 (7)(8)(9)(10)(11), ZFP36L2 (8,12,13), and ZFP36L3 (14). All TTP family members share high percentages of amino acid sequence identity within their TZF domains.…”

Members of the Tristetraprolin Family of Tandem CCCH Zinc Finger Proteins Exhibit CRM1-dependent Nucleocytoplasmic Shuttling

“…They are referred to here as CMG1 (15) (also known as TIS11B (16), ERF1 (17), BRF1 (18), or Berg36 (19)) and TIS11D (20) (also known as ERF2 (20) or BRF2 (21)). CMG1 and TIS11D each contain a TTP-like CCCH TZF domain, and they can, like TTP, destabilize the ARE-containing TNF␣, GM-CSF, and IL-3 mRNAs in co-transfection studies (1).…”