Identification and characterization of the Egr-1 gene product, a DNA-binding zinc finger protein induced by differentiation and growth signals.

Abstract

Egr-l is an immediate-early response gene induced by diverse signals that initiate growth and differentiation. Its cDNA sequence predicts a protein with zinc fingers. We have generated an antiserum to the Egr-1 gene product and identified it as an 80-kilodalton short-lived protein in serum-stimulated mouse fibroblasts. The rat Egr-l product has also been identified in nerve growth factor-induced PC12 cells. In addition, we show by cell fractionation and immunocytochemistry that the Egr-l protein is located in the nucleus. We also demonstrate that it is phosphorylated. In vitro-generated Egr-l protein binds with high affinity to the sequence CGCCCCCGC in a zinc-dependent manner.

SAGE transcript profiles for p53-dependent growth regulation

“…This well characterized transcriptional activator and repressor has been shown to be regulated in response to a wide array of growth regulatory stimuli, initially being described as an early growth response gene activated by serum (Sukhatme et al, 1988;Cao et al, 1990). Initial studies on EGR-1 appeared to correlate expression with enhanced cellular proliferation, however, more recently a role of EGR1 in cellular di erentiation has been proposed (Bains, 1996), similar to the role proposed for p21 WAF1/CIP1 in myogenic di erentiation (Liu et al, 1996).…”

Early Growth Response-1 Regulates Lipopolysaccharide-induced Suppressor of Cytokine Signaling-1 Transcription

“…2), consistent with the notion that a cis-acting element may be located within this region. Analysis of the S1 probe sequence suggested a putative binding site 5Ј-CGCCACCGC-3Ј (Ϫ849 to Ϫ841), which conforms to the Egr-1 consensus binding motif 5Ј-GCGGGGGCG-3Ј (33). Binding of Egr-1 to S1 was confirmed with the addition of antiEgr-1 antibody, which blocked the formation of the inducible complex.…”

“…Egr-1 is capable of regulating a number of genes involved in inflammation, including TNF-␣ (30, 31), tissue factor (29), and intercellular adhesion molecule-1 (32). Egr-1 preferentially binds to the GC-rich sequence 5Ј-GCGGGGGCG-3Ј (33)(34)(35) and is expressed in a wide variety of tissues including the thymus, muscle, bone, and parts of the nervous system during development (36). Egr-1-null mice are viable but have reduced body size and are sterile due to apparent defects in hormone regulation (37).…”

The EGF/TGFα response element within the TGFα promoter consists of a multi-complex regulatory element

“…Other EGF/TGFa responsive elements include the AP-1 transcription factor which has the minimal consensus sequence TGACTCA and binds jun family homodimers or jun ± fos heterodimers (Angel et al, 1987;Fisch et al, 1989;Curran and Franza, 1988;McDonnell et al, 1990). Moreover, GCrich motifs have also been reported to mediate EGF-responsiveness as in the Egr-1 (Cao et al, 1990;Sukhatme, 1991) and gastrin (Merchant et al, 1991) genes. These GC-rich motifs show weak homology to the consensus sequence for the transcription factor AP-2 which can mediate induction by both the cyclic AMP and protein kinase C pathways .…”