Early growth response 1 (EGR1) activation in initial stages of host–pathogen interactions

Banerji, Rajashri; Saroj, Sunil D.

doi:10.1007/s11033-021-06305-0

Cited by 20 publications

(21 citation statements)

References 56 publications

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“…This is consistent with our observation that a significant reduction in the upregulation of EGR1 was detected either in ERK1/2-knockdown cells or in the presence of an MEK/ERK inhibitor. On the contrary to the reported observation of JNK-mediated induction of EGR1 in stress response [ 39 ], this study showed that inhibition of either JNK or p38 enhanced the upregulation of EGR1 in coronavirus-infected cells, suggesting that JNK and p38 may function as negative regulators in coronavirus infection-induced upregulation of ERG1. The underlying mechanism is yet to be fully revealed, but it may point to the possibility that inhibition of JNK and p38 may reduce their competitive edge for the signals from their common upstream kinases with ERK1/2, leading to the enhanced upregulation of EGR1 in this context ( Figure 6 ).…”

Section: Discussioncontrasting

confidence: 99%

“…As a nuclear transcription factor, EGR1 regulates the expression of many cytokines in various physiological processes [ 30 , 31 ]. The regulatory roles of EGR1 in the induction of a number of antiviral cytokines/chemokines, including IFN-β, IL-8, ISG15 and CXCL2, were studied in EGR1-knockdown H1299 cells infected with IBV, PEDV and HCoV-229E, respectively.…”

Section: Resultsmentioning

confidence: 99%

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Modulation of viral replication, apoptosis and antiviral response by induction and mutual regulation of EGR and AP-1 family genes during coronavirus infection

Yuan

Fung

et al. 2022

Emerging Microbes & Infections

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Coronaviruses have evolved a variety of strategies to exploit normal cellular processes and signalling pathways for their efficient reproduction in a generally hostile cellular environment. One immediate-early response gene (IEG) family, the AP-1 gene family, was previously shown to be activated by coronavirus infection. In this study, we report that another IEG family, the EGR family, is also activated in cells infected with four different coronaviruses in three genera, i.e. gammacoronavirus infectious bronchitis virus (IBV), alphacoronaviruses porcine epidemic diarrhoea virus (PEDV) and human coronavirus-229E (HCoV-229E), and betacoronavirus HCoV-OC43. Knockdown of EGR1 reduced the expression of cJUN and cFOS, and knockdown of cJUN and/or cFOS reduced the expression of EGR1, demonstrating that these two IEG families may be cross-activated and mutual regulated. Furthermore, ERK1/2 was identified as an upstream kinase, and JNK and p38 as inhibitors of EGR1 activation in coronavirus-infected cells. However, upregulation of EGR family genes, in particular EGR1, appears to play a differential role in regulating viral replication, apoptosis and antiviral response. EGR1 was shown to play a limited role in regulation of coronavirus replication, and an anti-apoptotic role in cells infected with IBV or PEDV, but not in cells infected with HCoV-229E. Upregulation of EGR1 may also play a differential role in the regulation of antiviral response against different coronaviruses. This study reveals a novel regulatory network shared by different coronaviruses in the immediate-early response of host cells to infection.

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Section: Discussioncontrasting

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Modulation of viral replication, apoptosis and antiviral response by induction and mutual regulation of EGR and AP-1 family genes during coronavirus infection

Yuan

Fung

et al. 2022

Emerging Microbes & Infections

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“…Module 4 contained the key hub gene, EGR1 , which not only plays a vital role in regulating cell differentiation, growth, and survival, but is also a mediator of inflammatory gene expression and tumor cell metastasis. 40–42 Oxidative stress downregulates EGR1 expression in cardiomyocytes, 43 which is consistent with the findings of our study. Module 5 was composed of genes coding for upstream regulators of the ERK or AKT signaling pathway, including DUSP5.…”

Section: Discussionsupporting

confidence: 90%

Recovery of Dysregulated Genes in Cancer-Related Lower Limb Lymphedema After Supermicrosurgical Lymphaticovenous Anastomosis – A Prospective Longitudinal Cohort Study

Yang¹,

Huang²,

Wu³

et al. 2022

JIR

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“…The promoter region of the EGR1 gene contains transcription factor binding sites such as cyclic adenosine 3′, 5′-monophosphate (cAMP) response elements (CRE), an activator protein-1 (AP-1) binding site, an EGR binding site (EBS), specificity protein 1 (Sp1) elements, nuclear factor kappa B (NF-κB) binding site, and serum response elements (SREs; Figure 2). The CREs region can be occupied by members of the CREB protein family of transcription factors (Banerji and Saroj, 2021). The SREs function as binding sites for serum response factors (SRFs) and ternary complex factors (TCFs), such as Elk-1.…”

Section: Upstream Regulators Of Egr1mentioning

confidence: 99%

“…The EGR1 gene itself is highly conserved between numerous species including mouse, rat, chicken, zebrafish, chimpanzee, dog, cow, and human (Havis and Duprez, 2020). EGR1 is expressed in numerous cell types and is activated transiently and rapidly by a wide array of stimuli such as growth factors, cytokines, mitogens, apoptosis, oxygen deprivation, oxidative stress, shear stress, and tissue injury (Cao et al, 1990;Ouellette et al, 1990;Hirata et al, 1998;Yan et al, 1999;Nishi et al, 2002;Pines et al, 2005;Banerji and Saroj, 2021;Khachigian, 2021). EGR1 has a broad range of physiological functions and associates with numerous cellular signaling cascades and binding partners in response to stimulation.…”

Section: Introductionmentioning

confidence: 99%

Examining the role of EGR1 during viral infections

Lehman

Kehn-Hall

2022

Front. Microbiol.

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Early growth response 1 (EGR1) is a multifunctional mammalian transcription factor capable of both enhancing and/or inhibiting gene expression. EGR1 can be activated by a wide array of stimuli such as exposure to growth factors, cytokines, apoptosis, and various cellular stress states including viral infections by both DNA and RNA viruses. Following induction, EGR1 functions as a convergence point for numerous specialized signaling cascades and couples short-term extracellular signals to influence transcriptional regulation of genes required to initiate the appropriate biological response. The role of EGR1 has been extensively studied in both physiological and pathological conditions of the adult nervous system where it is readily expressed in various regions of the brain and is critical for neuronal plasticity and the formation of memories. In addition to its involvement in neuropsychiatric disorders, EGR1 has also been widely examined in the field of cancer where it plays paradoxical roles as a tumor suppressor gene or oncogene. EGR1 is also associated with multiple viral infections such as Venezuelan equine encephalitis virus (VEEV), Kaposi’s sarcoma-associated herpesvirus (KSHV), herpes simplex virus 1 (HSV-1), human polyomavirus JC virus (JCV), human immunodeficiency virus (HIV), and Epstein–Barr virus (EBV). In this review, we examine EGR1 and its role(s) during viral infections. First, we provide an overview of EGR1 in terms of its structure, other family members, and a brief overview of its roles in non-viral disease states. We also review upstream regulators of EGR1 and downstream factors impacted by EGR1. Then, we extensively examine EGR1 and its roles, both direct and indirect, in regulating replication of DNA and RNA viruses.

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Early growth response 1 (EGR1) activation in initial stages of host–pathogen interactions

Cited by 20 publications

References 56 publications

Modulation of viral replication, apoptosis and antiviral response by induction and mutual regulation of EGR and AP-1 family genes during coronavirus infection

Modulation of viral replication, apoptosis and antiviral response by induction and mutual regulation of EGR and AP-1 family genes during coronavirus infection

Recovery of Dysregulated Genes in Cancer-Related Lower Limb Lymphedema After Supermicrosurgical Lymphaticovenous Anastomosis – A Prospective Longitudinal Cohort Study

Examining the role of EGR1 during viral infections

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