EGR1

What is EGR1 Protein?

EGR1 gene (early growth response 1) is a protein coding gene which situated on the long arm of chromosome 5 at locus 5q31. The EGR1 protein, also known as the Early Growth Response 1 protein, is a transcription factor belonging to the C2H2 type zinc finger protein family. It functions primarily in the nucleus and is able to act as a transcriptional regulator, recognizing and binding promoter regions of target genes and regulating the transcription of these genes. EGR1 plays a key role in a variety of biological processes, including cell proliferation, differentiation, migration, and apoptosis, and is an important regulator of cell response to a variety of external stimuli. The EGR1 protein is consisted of 543 amino acids and EGR1 molecular weight is approximately 57.5 kDa.

What is the Function of EGR1 Protein?

EGR1 is able to recognize and bind to specific DNA sequences in promoter regions of target genes, thereby regulating the transcription of these genes. EGR1 plays a key role in cell response to a variety of stimuli, including responses to growth factors, DNA damage, and ischemia. It is involved in regulating cell survival, proliferation, and death, and helps prevent tumor formation by activating the expression of genes such as p53/TP53 and TGFB1. In addition, EGR1 is involved in regulating the mitotic process and normal proliferation of liver cells after partial resection, as well as the response to ischemia and hypoxia. EGR1 also regulates the expression of genes associated with inflammatory processes and repair after tissue damage, such as IL1B and CXCL2.

EGR1 Related Signaling Pathway

EGR1 can promote cell proliferation by activating MAPK signaling pathway, which involves proteins such as RAS, RAF, MEK and ERK, and has an important influence on the expression and activity of EGR1. In some cases, EGR1 can activate tumor suppressor genes such as p21Waf1/Cip1, PTEN and BRCA1, which play an anti-tumor role by promoting apoptosis and inhibiting tumor cell invasion and metastasis. EGR1 can promote the invasion and metastasis of tumor cells by activating the expression of EMT-related genes such as SNAIL and SLUG. EGR1 can promote the apoptosis of tumor cells by directly binding and activating the expression of BAX, NAG1 and PTEN genes.

EGR1 Related Diseases

EGR1 is closely related to the occurrence, development, invasion and metastasis of tumors, and may be involved in tumor cell proliferation, angiogenesis and resistance to therapy. The expression level of EGR1 in the brain of patients with Alzheimer's disease (AD) is increased, which is closely related to the onset or progression of AD. EGR1 may be involved in the pathogenesis of AD by influencing the production of amyloid beta peptide, phosphorylation of tau protein, cholinergic nervous system dysfunction, cellular inflammation, and regulation of aging processes. EGR1 plays an important role in the process of renal fibrosis in diabetic nephropathy. EGR1 is related to ovarian senescence, and may affect follicular atresia and ovarian function decline by regulating granulosa cell proliferation and apoptosis. EGR1 can inhibit the expression of pro-inflammatory genes in macrophages, and affect the initiation, maintenance and resolution of inflammatory processes.

Fig1. Schematic diagram of the EGR1 functional model involving known possible mechanisms of EGR1 in inflammatory lung diseases. (Kang Zou, 2023)

Bioapplications of EGR1

EGR1 is used as a biomarker in many diseases, such as cancer and liver and bile diseases, and by detecting its expression level, doctors can assess patients' conditions and guide precise treatment. EGR1 can be an important target for drug development, especially in the field of tumor therapy. Inhibition of the EGR1 signaling pathway can inhibit the growth and metastasis of tumor cells, and EGR1 inhibitors such as CDK4/6 inhibitors and EGFR inhibitors have shown efficacy in a variety of tumor therapies. EGR1 plays a role in the diagnosis and treatment of tumors, and the detection of its expression level is helpful for the identification of tumors and the evaluation of treatment response.

Case Study 1: Jinrun Zhou, 2022

Myocardial apoptosis induced by myocardial ischemia and hyperlipemia are the main causes of high mortality of cardiovascular diseases. It is not clear whether there is a common mechanism responsible for these two kinds of cardiomyocyte apoptosis. Previous studies demonstrated that early growth response protein 1 (EGR-1) has a pro-apoptotic effect on cardiomyocytes under various stress conditions. Here, this study revealed that EGR-1 is also involved in cardiomyocyte apoptosis induced by both ischemia and high-fat, but how EGR-1 enters the nucleus and whether nuclear EGR-1 (nEGR-1) has a universal effect on cardiomyocyte apoptosis are still unknown. By analyzing the phosphorylation sites and nucleation information of EGR-1, researchers constructed different mutant plasmids to confirm that the nucleus location of EGR-1 requires Ser501 phosphorylation and regulated by JNK. Furthermore, the pro-apoptotic effect of nEGR-1 was further explored through genetic methods.

Fig1. H9c2 cells were treated with BSA and PA for 3 h, the localization of EGR-1 was detected by immunofluorescence assay.

Fig2. Homology comparison of Ser501 site of EGR-1 among different species.

Case Study 2: Hua Wang, 2021

Porcine epidemic diarrhea virus (PEDV) is a globally distributed alphacoronavirus that has reemerged lately, resulting in large economic losses. During viral infection, type I interferon (IFN-I) plays a vital role in the antiviral innate immunity. However, PEDV has evolved strategies to limit IFN-I production. To suppress virus replication, the host must activate IFN-stimulated genes and some host restriction factors to circumvent viral replication. This study observed that PEDV infection induced early growth response gene 1 (EGR1) expression in PEDV-permissive cells. EGR1 overexpression remarkably suppressed PEDV replication. In contrast, depletion of EGR1 led to a significant increase in viral replication. EGR1 suppressed PEDV replication by directly binding to the IFN-regulated antiviral (IRAV) promoter and upregulating IRAV expression. A detailed analysis revealed that IRAV interacts and colocalizes with the PEDV nucleocapsid (N) protein, inducing N protein degradation via the E3 ubiquitin ligase MARCH8 to catalyze N protein ubiquitination. Knockdown of endogenous MARCH8 significantly reversed IRAV-mediated N protein degradation.

Fig3. PEDV infection induces EGR1 expression.

Fig4. Vero cells were infected with PEDV (MOI of 0.01) or mock infected and were harvested at 20 h postinfection.

EGR1 has several biochemical functions, for example, DNA binding,RNA polymerase II core promoter sequence-specific DNA binding,RNA polymerase II regulatory region sequence-specific DNA binding. Some of the functions are cooperated with other proteins, some of the functions could acted by EGR1 itself. We selected most functions EGR1 had, and list some proteins which have the same functions with EGR1. You can find most of the proteins on our site.

EGR1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with EGR1 here. Most of them are supplied by our site. Hope this information will be useful for your research of EGR1.

CDKN2A;CTNNB1;SNAI1;SP1;SUMO1;SREBF2;nos;astD;MAGEB2;MED6;DNAJC8