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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

EGR1  -  early growth response 1

Homo sapiens

Synonyms: AT225, EGR-1, Early growth response protein 1, G0S30, KROX-24, ...


EGR1 was identified in 1985 as a 3.4 kb mRNA showing rapid differential expression in cultured human peripheral blood mononuclear cells that had been treated with the lectin, Concanavalin-A, and cycloheximide [1]. It was one of a set of putative G0/G1 switch (G0S) regulatory genes (and was named G0S30). A close sequence similarity to the mRNAs of rat NGF1A and mouse Krox24 was reported in 1990 [2]. Rapid induction by Concanavalin-A alone was reported in 1996, as was an apparent inhibition by "stealth" concentrations (50 nM) of a complementary oligonucleotide . The ineffectiveness of higher oligonucleotide concentrations was deemed due to activation of an intracellular defense system against foreign nucleic acids [3]. In 1997 EGR1/G0S30 was reported to be one of several genes whose transcripts increase in "stressed" cells (i.e. the stress of isolation of the cells from human subjects). The cells had first to be "rested" in culture for 24 h in order to demonstrate most clearly the brisk (30 min) elevation of mRNA in response to Concanavalin-A [4]. It was speculated that the stress response is part of a pan-genic (and pan-nongenic) transcriptional response directed at foreign nucleic acids [5].


Disease relevance of EGR1


Psychiatry related information on EGR1


High impact information on EGR1

  • The amino acid sequence of the predicted polypeptide shows significant homology to two growth regulated mammalian polypeptides, EGR1 and EGR2 [12].
  • This structure-based strategy was tested by construction of a fusion protein, ZFHD1, that contained zinc fingers 1 and 2 from Zif268, a short polypeptide linker, and the homeodomain from Oct-1 [13].
  • Analyzing the GLI complex and comparing it with Zif268 offers new perspectives on Zn finger-DNA recognition [14].
  • In transient transfection assays, the WT1 protein functioned as a repressor of transcription when bound to the EGR-1 site [15].
  • The binding sites obtained were similar to the sequence recognized by the early growth response-1 (EGR-1) gene product, a zinc finger-containing protein that is induced by mitogenic stimuli [16].

Chemical compound and disease context of EGR1


Biological context of EGR1

  • This zinc-finger region, which is thought to bind DNA in a sequence-specific manner, is similar (greater than 80% on the amino acid level) to two previously described transcription factors pAT 225/EGR1 and pAT 591/EGR2 [22].
  • We report that WT1, but not EGR1, can bind specific Igf-2 exonic RNA sequences, and that the zinc fingers are required for this interaction [23].
  • WT1 encodes a transcription factor which binds to the EGR1 consensus sequence, mediating transcriptional repression [24].
  • By hybridizing probes to metaphase cells with overlapping deletions involving 5q31, we have narrowed the critical region to a small segment of 5q31 containing the EGR1 gene [6].
  • Transactivation of the EGR1 gene contributes to mutant p53 gain of function [25].

Anatomical context of EGR1


Associations of EGR1 with chemical compounds

  • The minor groove binder chromomycin A3 inhibited EGR1 complex formation but resulted in a smaller increase of the TBP complex [8].
  • Finally, we demonstrate that dexamethasone, an inhibitor of monocytic differentiation, blocks the associated increases in EGR-1 and EGR-2 expression [29].
  • Preincubation with cycloheximide was associated with superinduction of JUN and EGR1 in x-irradiated cells [30].
  • Inhibition of protein kinase C activity by prolonged stimulation with phorbol 12-myristate 13-acetate or the protein kinase inhibitor H7 prior to irradiation attenuated the increase in EGR1 and JUN transcripts [30].
  • The most abundant splicing variants contain a nine-nucleotide insertion encoding lysine, threonine, and serine (KTS) in the H-C link region between the third and fourth WT1 zinc fingers which disrupts binding to a previously defined WT1-EGR1 binding site [31].
  • These data suggest that bombesin enhances Egr-1 expression leading to increased hPar1 transcription, thereby increasing PAR1 expression and function [32].

Physical interactions of EGR1

  • We hypothesize that CpG hypomethylation in the heparanase promoter coupled with up-regulation of EGR1 levels may induce heparanase expression in human prostate cancer [33].
  • Reporter constructs bearing the EGR-1 binding segment of the TGF-beta 1 promoter was activated 4- to 6-fold relative to a control reporter in either HT-1080 cells that stably expressed or parental cells cotransfected with an EGR-1 expression vector [34].
  • EGR-1 binds to the ATF3 promoter as assessed by gel shift assay [18].
  • Our findings suggest that high levels of EGR1 coupled with low levels of NAB2 can result in high, unrestrained EGR1 transcriptional activity in human prostate cancers [35].
  • Egr-1 binding to a recognition sequence in the TIMP-1 promoter was demonstrated in gel retardation and reporter gene assays [36].

Enzymatic interactions of EGR1


Regulatory relationships of EGR1


Other interactions of EGR1

  • In the absence of p53, WT1 acts as a potent transcriptional activator of the early growth response gene 1 (EGR1) site, rather than a transcriptional repressor [24].
  • Early growth response gene 1 modulates androgen receptor signaling in prostate carcinoma cells [7].
  • Our results suggest that Egr-1 induction is a unique property of TGZ compared with other PPAR gamma ligands and is independent of PPAR gamma activation [39].
  • The blocking of egr-1 with an antisense sequence prevented H. pylori-induced Egr-1 and CD44 protein expression [43].
  • In NG108-15 cells, dbcAMP excerted a strong enhancing activity on the transactivation properties of NGFI-C while this was not observed when cells were transfected with NGFI-A [44].
  • We provide novel evidence for a complex c-Jun-mediated mechanism that is essential for inducible EGR-1 expression [45].

Analytical, diagnostic and therapeutic context of EGR1

  • Moreover, chromatin immunoprecipitation analysis indicates that mutant p53 is physically associated with the EGR1 promoter [25].
  • Increased EGR1 protein expression was confirmed by Western blot analysis [46].
  • We performed methylation-specific PCR targeting the CpG sites within the core-binding consensus motifs of EGR1 (GGCG) and Sp1 (GGGCGG) [27].
  • We propose that gene therapy involving sustained EGR-1 expression may constitute a novel therapeutic principle in the treatment of cancer due to the simultaneous induction of multiple pathways of antiangiogenesis, growth arrest, and apoptosis induction in proliferating cells leading to preferential inhibition of angiogenesis and tumor growth [47].
  • Egr-1 expression was assayed by immunoblotting and electrophoretic mobility shift assays using H. pylori-stimulated AGS cells [43].


  1. cDNA cloning of mRNAS which increase rapidly in human lymphocytes cultured with concanavalin-A and cycloheximide. Forsdyke, D.R. Biochem. Biophys. Res. Commun. (1985) [Pubmed]
  2. A set of human putative lymphocyte G0/G1 switch genes includes genes homologous to rodent cytokine and zinc finger protein-encoding genes. Siderovski, D.P., Blum, S., Forsdyke, R.E., Forsdyke, D.R. DNA. Cell. Biol. (1990) [Pubmed]
  3. A "stealth" approach to inhibition of lymphocyte activation by oligonucleotide complementary to the putative G0/G1 switch regulatory gene G0S30/EGR1/NGFI-A. Cristillo, A.D., Heximer, S.P., Forsdyke, D.R. DNA. Cell. Biol. (1996) [Pubmed]
  4. Cyclosporin A inhibits early mRNA expression of G0/G1 switch gene 2 (G0S2) in cultured human blood mononuclear cells. Cristillo, A.D., Heximer, S.P., Russell, L., Forsdyke, D.R. DNA. Cell. Biol. (1997) [Pubmed]
  5. Immunity as a function of the unicellular state: implications of emerging genomic data. Forsdyke, D.R., Madill, C.A., Smith, S.D. Trends. Immunol. (2002) [Pubmed]
  6. Cytogenetic and molecular delineation of the smallest commonly deleted region of chromosome 5 in malignant myeloid diseases. Le Beau, M.M., Espinosa, R., Neuman, W.L., Stock, W., Roulston, D., Larson, R.A., Keinanen, M., Westbrook, C.A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  7. Early growth response gene 1 modulates androgen receptor signaling in prostate carcinoma cells. Yang, S.Z., Abdulkadir, S.A. J. Biol. Chem. (2003) [Pubmed]
  8. Effect of DNA-binding drugs on early growth response factor-1 and TATA box-binding protein complex formation with the herpes simplex virus latency promoter. Chiang, S.Y., Welch, J.J., Rauscher, F.J., Beerman, T.A. J. Biol. Chem. (1996) [Pubmed]
  9. Cellular gene expression upon human immunodeficiency virus type 1 infection of CD4(+)-T-cell lines. van 't Wout, A.B., Lehrman, G.K., Mikheeva, S.A., O'Keeffe, G.C., Katze, M.G., Bumgarner, R.E., Geiss, G.K., Mullins, J.I. J. Virol. (2003) [Pubmed]
  10. Expression of the transcription factor Zif268 in the temporal cortex of monkeys during visual paired associate learning. Okuno, H., Miyashita, Y. Eur. J. Neurosci. (1996) [Pubmed]
  11. Expression of the immediate-early gene-encoded protein Egr-1 (zif268) during in vitro classical conditioning. Mokin, M., Keifer, J. Learn. Mem. (2005) [Pubmed]
  12. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Call, K.M., Glaser, T., Ito, C.Y., Buckler, A.J., Pelletier, J., Haber, D.A., Rose, E.A., Kral, A., Yeger, H., Lewis, W.H. Cell (1990) [Pubmed]
  13. Structure-based design of transcription factors. Pomerantz, J.L., Sharp, P.A., Pabo, C.O. Science (1995) [Pubmed]
  14. Crystal structure of a five-finger GLI-DNA complex: new perspectives on zinc fingers. Pavletich, N.P., Pabo, C.O. Science (1993) [Pubmed]
  15. Transcriptional repression mediated by the WT1 Wilms tumor gene product. Madden, S.L., Cook, D.M., Morris, J.F., Gashler, A., Sukhatme, V.P., Rauscher, F.J. Science (1991) [Pubmed]
  16. Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence. Rauscher, F.J., Morris, J.F., Tournay, O.E., Cook, D.M., Curran, T. Science (1990) [Pubmed]
  17. Enhanced EGR1 activity promotes the growth of prostate cancer cells in an androgen-depleted environment. Yang, S.Z., Eltoum, I.A., Abdulkadir, S.A. J. Cell. Biochem. (2006) [Pubmed]
  18. Activating transcription factor 3 and early growth response 1 are the novel targets of LY294002 in a phosphatidylinositol 3-kinase-independent pathway. Yamaguchi, K., Lee, S.H., Kim, J.S., Wimalasena, J., Kitajima, S., Baek, S.J. Cancer Res. (2006) [Pubmed]
  19. Activation of serine/threonine protein kinases and early growth response 1 gene expression by tumor necrosis factor in human myeloid leukemia cells. Saleem, A., Yuan, Z.M., Taneja, N., Rubin, E., Kufe, D.W., Kharbanda, S.M. J. Immunol. (1995) [Pubmed]
  20. 1,1-Bis(3'-indolyl)-1-(p-substitutedphenyl)methanes are peroxisome proliferator-activated receptor gamma agonists but decrease HCT-116 colon cancer cell survival through receptor-independent activation of early growth response-1 and nonsteroidal anti-inflammatory drug-activated gene-1. Chintharlapalli, S., Papineni, S., Baek, S.J., Liu, S., Safe, S. Mol. Pharmacol. (2005) [Pubmed]
  21. Glucose intake induces an increase in activator protein 1 and early growth response 1 binding activities, in the expression of tissue factor and matrix metalloproteinase in mononuclear cells, and in plasma tissue factor and matrix metalloproteinase concentrations. Aljada, A., Ghanim, H., Mohanty, P., Syed, T., Bandyopadhyay, A., Dandona, P. Am. J. Clin. Nutr. (2004) [Pubmed]
  22. Clone pAT 133 identifies a gene that encodes another human member of a class of growth factor-induced genes with almost identical zinc-finger domains. Müller, H.J., Skerka, C., Bialonski, A., Zipfel, P.F. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  23. RNA binding by the Wilms tumor suppressor zinc finger proteins. Caricasole, A., Duarte, A., Larsson, S.H., Hastie, N.D., Little, M., Holmes, G., Todorov, I., Ward, A. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  24. Physical and functional interaction between WT1 and p53 proteins. Maheswaran, S., Park, S., Bernard, A., Morris, J.F., Rauscher, F.J., Hill, D.E., Haber, D.A. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  25. Transactivation of the EGR1 gene contributes to mutant p53 gain of function. Weisz, L., Zalcenstein, A., Stambolsky, P., Cohen, Y., Goldfinger, N., Oren, M., Rotter, V. Cancer Res. (2004) [Pubmed]
  26. Molecular cloning of a novel human cDNA encoding a zinc finger protein that binds to the interleukin-3 promoter. Koyano-Nakagawa, N., Nishida, J., Baldwin, D., Arai, K., Yokota, T. Mol. Cell. Biol. (1994) [Pubmed]
  27. Promoter CpG hypomethylation and transcription factor EGR1 hyperactivate heparanase expression in bladder cancer. Ogishima, T., Shiina, H., Breault, J.E., Terashima, M., Honda, S., Enokida, H., Urakami, S., Tokizane, T., Kawakami, T., Ribeiro-Filho, L.A., Fujime, M., Kane, C.J., Carroll, P.R., Igawa, M., Dahiya, R. Oncogene (2005) [Pubmed]
  28. Modulation of early growth response (EGR) transcription factor-dependent gene expression by using recombinant adenovirus. Ehrengruber, M.U., Muhlebach, S.G., Söhrman, S., Leutenegger, C.M., Lester, H.A., Davidson, N. Gene (2000) [Pubmed]
  29. Expression of the early growth response 1 and 2 zinc finger genes during induction of monocytic differentiation. Kharbanda, S., Nakamura, T., Stone, R., Hass, R., Bernstein, S., Datta, R., Sukhatme, V.P., Kufe, D. J. Clin. Invest. (1991) [Pubmed]
  30. Protein kinase C mediates x-ray inducibility of nuclear signal transducers EGR1 and JUN. Hallahan, D.E., Sukhatme, V.P., Sherman, M.L., Virudachalam, S., Kufe, D., Weichselbaum, R.R. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  31. DNA recognition by splicing variants of the Wilms' tumor suppressor, WT1. Drummond, I.A., Rupprecht, H.D., Rohwer-Nutter, P., Lopez-Guisa, J.M., Madden, S.L., Rauscher, F.J., Sukhatme, V.P. Mol. Cell. Biol. (1994) [Pubmed]
  32. Transcriptional regulation of human protease-activated receptor 1: a role for the early growth response-1 protein in prostate cancer. Salah, Z., Maoz, M., Pizov, G., Bar-Shavit, R. Cancer Res. (2007) [Pubmed]
  33. Increased heparanase expression is caused by promoter hypomethylation and up-regulation of transcriptional factor early growth response-1 in human prostate cancer. Ogishima, T., Shiina, H., Breault, J.E., Tabatabai, L., Bassett, W.W., Enokida, H., Li, L.C., Kawakami, T., Urakami, S., Ribeiro-Filho, L.A., Terashima, M., Fujime, M., Igawa, M., Dahiya, R. Clin. Cancer Res. (2005) [Pubmed]
  34. Transcription factor EGR-1 suppresses the growth and transformation of human HT-1080 fibrosarcoma cells by induction of transforming growth factor beta 1. Liu, C., Adamson, E., Mercola, D. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  35. Frequent and early loss of the EGR1 corepressor NAB2 in human prostate carcinoma. Abdulkadir, S.A., Carbone, J.M., Naughton, C.K., Humphrey, P.A., Catalona, W.J., Milbrandt, J. Hum. Pathol. (2001) [Pubmed]
  36. Transcription factor early growth response 1 activity up-regulates expression of tissue inhibitor of metalloproteinases 1 in human synovial fibroblasts. Aicher, W.K., Alexander, D., Haas, C., Kuchen, S., Pagenstecher, A., Gay, S., Peter, H.H., Eibel, H. Arthritis Rheum. (2003) [Pubmed]
  37. Proximal cyclic AMP response element is essential for exendin-4 induction of rat EGR-1 gene. Kang, J.H., Kim, M.J., Jang, H.I., Koh, K.H., Yum, K.S., Rhie, D.J., Yoon, S.H., Hahn, S.J., Kim, M.S., Jo, Y.H. Am. J. Physiol. Endocrinol. Metab. (2007) [Pubmed]
  38. Early growth response gene 1 (EGR1) is deleted in estrogen receptor-negative human breast carcinoma. Ronski, K., Sanders, M., Burleson, J.A., Moyo, V., Benn, P., Fang, M. Cancer (2005) [Pubmed]
  39. Troglitazone, a peroxisome proliferator-activated receptor gamma (PPAR gamma ) ligand, selectively induces the early growth response-1 gene independently of PPAR gamma. A novel mechanism for its anti-tumorigenic activity. Baek, S.J., Wilson, L.C., Hsi, L.C., Eling, T.E. J. Biol. Chem. (2003) [Pubmed]
  40. Amyloid peptide-induced cytokine and chemokine expression in THP-1 monocytes is blocked by small inhibitory RNA duplexes for early growth response-1 messenger RNA. Giri, R.K., Selvaraj, S.K., Kalra, V.K. J. Immunol. (2003) [Pubmed]
  41. Early growth response proteins (EGR) and nuclear factors of activated T cells (NFAT) form heterodimers and regulate proinflammatory cytokine gene expression. Decker, E.L., Nehmann, N., Kampen, E., Eibel, H., Zipfel, P.F., Skerka, C. Nucleic Acids Res. (2003) [Pubmed]
  42. Egr-1 mediates hypoxia-inducible transcription of the NDRG1 gene through an overlapping Egr-1/Sp1 binding site in the promoter. Zhang, P., Tchou-Wong, K.M., Costa, M. Cancer Res. (2007) [Pubmed]
  43. Helicobacter pylori activates the early growth response 1 protein in gastric epithelial cells. Abdel-Latif, M.M., Windle, H.J., Fitzgerald, K.A., Ang, Y.S., Eidhin, D.N., Li-Weber, M., Sabra, K., Kelleher, D. Infect. Immun. (2004) [Pubmed]
  44. Transcriptional activation of human choline acetyltransferase by AP2- and NGF-induced factors. Quirin-Stricker, C., Mauvais, C., Schmitt, M. Brain Res. Mol. Brain Res. (1997) [Pubmed]
  45. Transcriptional regulation of EGR-1 by the interleukin-1-JNK-MKK7-c-Jun pathway. Hoffmann, E., Ashouri, J., Wolter, S., Doerrie, A., Dittrich-Breiholz, O., Schneider, H., Wagner, E.F., Troppmair, J., Mackman, N., Kracht, M. J. Biol. Chem. (2008) [Pubmed]
  46. Changes in differential gene expression because of warm ischemia time of radical prostatectomy specimens. Dash, A., Maine, I.P., Varambally, S., Shen, R., Chinnaiyan, A.M., Rubin, M.A. Am. J. Pathol. (2002) [Pubmed]
  47. Sustained expression of early growth response protein-1 blocks angiogenesis and tumor growth. Lucerna, M., Pomyje, J., Mechtcheriakova, D., Kadl, A., Gruber, F., Bilban, M., Sobanov, Y., Schabbauer, G., Breuss, J., Wagner, O., Bischoff, M., Clauss, M., Binder, B.R., Hofer, E. Cancer Res. (2006) [Pubmed]
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