Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Early Growth Response 3 (EGR3)

  • Bianca PfaffensellerEmail author
  • Bianca Wollenhaupt-Aguiar
  • Fábio Klamt
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101638


Historical Background

In 1991, the human EGR3 gene was first described by Patwardhan and colleagues. The EGR3 is an immediate early growth response gene first observed to be induced by mitogenic stimulation of rodent and human fibroblasts and monkey kidney epithelial cell line. The EGR3 cDNA sequence infers a 387 amino acid protein, and the EGR3 gene has a single intron and the cytogenetic location is 8p21.3 (Patwardhan et al. 1991).

The EGR3 is part of the early growth response (EGR) transcription factors family, which has five members: EGR1 (also known as ZIF268, NGFI-A, TIS8, KROX-24, or ZENK), EGR2 (also known as KROX-20), EGR3 (also known as PILOT), EGR4 (also known as NGFI-C or pAT133), and the product of the Wilms’ tumor gene, WT-1 (Pérez-Cadahía et al. 2011). The EGR family is characterized as immediate early genes (IEG) encoded transcription factors and has a highly conserved DNA-binding domain containing three zinc-finger motifs...
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  1. Eldredge LC, Gao XM, Quach DH, Li L, Han X, Lomasney J, et al. Abnormal sympathetic nervous system development and physiological dysautonomia in Egr3-deficient mice. Development. 2008;135:2949–57.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Gallitano AL, Tillman R, Dinu V, Geller B. Family-based association study of early growth response gene 3 with child bipolar I disorder. J Affect Disord. 2012;138:387–96.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Gallitano-Mendel A, Izumi Y, Tokuda K, Zorumski CF, Howell MP, Muglia LJ, et al. The immediate early gene early growth response gene 3 mediates adaptation to stress and novelty. Neuroscience. 2007;148:633–43.CrossRefPubMedGoogle Scholar
  4. Gao X, Daugherty RL, Tourtellotte WG. Regulation of low affinity neurotrophin receptor (p75(NTR)) by early growth response (Egr) transcriptional regulators. Mol Cell Neurosci. 2007;36:501–14.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Hippenmeyer S, Shneider NA, Birchmeier C, Burden SJ, Jessell TM, Arber S. A role for neuregulin1 signaling in muscle spindle differentiation. Neuron. 2002;36:1035–49.CrossRefPubMedGoogle Scholar
  6. Li L, Carter J, Gao X, Whitehead J, Tourtellotte WG. The neuroplasticity-associated arc gene is a direct transcriptional target of early growth response (Egr) transcription factors. Mol Cell Biol. 2005;25:10286–300.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Li L, Yun SH, Keblesh J, Trommer BL, Xiong H, Radulovic J, et al. Egr3, a synaptic activity regulated transcription factor that is essential for learning and memory. Mol Cell Neurosci. 2007;35:76–88.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Liao F, Ji MY, Shen L, Qiu S, Guo XF, Dong WG. Decreased EGR3 expression is related to poor prognosis in patients with gastric cancer. J Mol Histol. 2013;44:463–8.  https://doi.org/10.1007/s10735-013-9493-8.CrossRefPubMedGoogle Scholar
  9. Liu D, Evans I, Britton G, Zachary I. The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis. Oncogene. 2008;27:2989–98.CrossRefPubMedGoogle Scholar
  10. Morris ME, Viswanathan N, Kuhlman S, Davis FC, Weitz CJ. A screen for genes induced in the suprachiasmatic nucleus by light. Science. 1998;279:1544–7.CrossRefPubMedGoogle Scholar
  11. O’Donovan KJ, Tourtellotte WG, Millbrandt J, Baraban JM. The EGR family of transcription-regulatory factors: progress at the interface of molecular and systems neuroscience. Trends Neurosci. 1999;22:167–73.CrossRefPubMedGoogle Scholar
  12. Patwardhan S, Gashler A, Siegel MG, Chang LC, Joseph LJ, Shows TB, et al. EGR3, a novel member of the Egr family of genes encoding immediate-early transcription factors. Oncogene. 1991;6:917–28.PubMedGoogle Scholar
  13. Pérez-Cadahía B, Drobic B, Davie JR. Activation and function of immediate-early genes in the nervous system. Biochem Cell Biol. 2011;89:61–73.  https://doi.org/10.1139/O10-138.CrossRefPubMedGoogle Scholar
  14. Pfaffenseller B, da Silva Magalhães PV, De Bastiani MA, Castro MA, Gallitano AL, Kapczinski F, et al. Differential expression of transcriptional regulatory units in the prefrontal cortex of patients with bipolar disorder: potential role of early growth response gene 3. Transl Psychiatry. 2016;6:e805.  https://doi.org/10.1038/tp.2016.78.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Pio R, Jia Z, Baron VT, Mercola D. UCI NCI SPECS consortium of the strategic partners for the evaluation of cancer signatures-prostate cancer. Early growth response 3 (Egr3) is highly over-expressed in non-relapsing prostate cancer but not in relapsing prostate cancer. PLoS One. 2013;8:e54096.  https://doi.org/10.1371/journal.pone.0054096.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Roberts DS, Hu Y, Lund IV, Brooks-Kayal AR, Russek SJ. Brain-derived neurotrophic factor (BDNF)-induced synthesis of early growth response factor 3 (Egr3) controls the levels of type A GABA receptor alpha 4 subunits in hippocampal neurons. J Biol Chem. 2006;281:29431–5.CrossRefPubMedGoogle Scholar
  17. Safford M, Collins S, Lutz MA, Allen A, Huang CT, Kowalski J, et al. Egr-2 and Egr-3 are negative regulators of T cell activation. Nature Immun. 2005;6:472–80. Erratum: Nature Immun. 2005;6:737CrossRefPubMedGoogle Scholar
  18. Weigelt K, Carvalho LA, Drexhage RC, Wijkhuijs A, de Wit H, van Beveren NJ, et al. TREM-1 and DAP12 expression in monocytes of patients with severe psychiatric disorders. EGR3, ATF3 and PU.1 as important transcription factors. Brain Behav Immun. 2011;25:1162–9.  https://doi.org/10.1016/j.bbi.2011.03.006.CrossRefPubMedGoogle Scholar
  19. Yamada K, Gerber DJ, Iwayama Y, Ohnishi T, Ohba H, Toyota T, et al. Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia. Proc Natl Acad Sci USA. 2007;104:2815–20.PubMedPubMedCentralCrossRefGoogle Scholar
  20. Yamagata K, Kaufmann WE, Lanahan A, Papapavlou M, Barnes CA, Andreasson KI, et al. Egr3/Pilot, a zinc finger transcription factor, is rapidly regulated by activity in brain neurons and colocalizes with Egr1/zif268. Learn Mem. 1994;1:140–52.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Bianca Pfaffenseller
    • 1
    • 2
    Email author
  • Bianca Wollenhaupt-Aguiar
    • 1
    • 2
  • Fábio Klamt
    • 3
  1. 1.Laboratory of Cellular Biochemistry, Department of Biochemistry, Institute of Basic Health Science (ICBS)Federal University of Rio Grande do Sul (UFRGS)Porto AlegreBrazil
  2. 2.Laboratory of Molecular PsychiatryHospital de Clínicas de Porto Alegre (HCPA)Porto AlegreBrazil
  3. 3.Laboratory of Cellular Biochemistry, Department of BiochemistryInstitute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS)St Porto AlegreBrazil