Page 276 - Read Online

Magee et al. Hepatoma Res 2017;3:268-77 Hepatoma Research
DOI: 10.20517/2394-5079.2017.36
www.hrjournal.net
Review Open Access

Role of early growth response 1 in liver

metabolism and liver cancer

Nancy Magee, Yuxia Zhang

Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Correspondence to: Dr. Yuxia Zhang, Department of Pharmacology, Toxicology & Therapeutics, University of Kansas Medical Center, 4089 HLSIC,
MS 1018, 3901 Rainbow Blvd, Kansas City, KS 66160, USA. E-mail: lzhang5@kumc.edu
How to cite this article: Magee N, Zhang Y. Role of early growth response 1 in liver metabolism and liver cancer. Hepatoma Res 2017;3:268-77.

ABSTRACT

Article history: The liver is an essential organ for nutrient and drug metabolism - possessing the remarkable
Received: 15 Aug 2017 ability to sense environmental and metabolic stimuli and provide an optimally adaptive
First decision: 25 Sep 2017 response. Early growth response 1 (Egr1), an immediate early transcriptional factor which
acts as a coordinator of the complex response to stress, is induced during liver injury and
Revised: 10 Oct 2017
Accepted: 7 Nov 2017 controls the expression of a wide range of genes involved in metabolism, cell proliferation, and
inflammation. In support of an important role of Egr1 in liver injury and repair, deficiency of
Published: 20 Nov 2017
Egr1 delays liver regeneration process. The known upstream regulators of Egr1 include, but
Key words: are not limited to, growth factors (e.g. transforming growth factor β1, platelet-derived growth
Early growth response 1, factor, epidermal growth factor, hepatocyte growth factor), nuclear receptors (e.g. hepatocyte
liver, nuclear factor 4α, small heterodimer partner, peroxisome proliferator-activated receptor-γ),
fibrosis, and other transcription factors (e.g. Sp1, E2F transcription factor 1). Research efforts using
injury, various animal models such as fatty liver, liver injury, and liver fibrosis contribute greatly
liver cancer to the elucidation of Egr1 function in the liver. Hepatocellular carcinoma (HCC) represents
the second leading cause of cancer mortality worldwide due to the heterogeneity and the
late stage at which cancer is generally diagnosed. Recent studies highlight the involvement
of Egr1 in HCC development. The purpose of this review is to summarize current studies
pertaining to the role of Egr1 in liver metabolism and liver diseases including liver cancer.

INTRODUCTION it is not elusive that zinc metal is crucial to the
function of Egr1, such as nuclear localization .
[3]
Early growth response 1 (Egr1) is an immediate early, Specifically, two of three zinc fingers interact with
zinc finger transcription factor that was first identified the nuclear localization sequence to promote Egr1
based upon its induction by nerve growth factor (NGF) nuclear localization . Depletion of the zinc metal
[3]
in rat PC12 cells, which is why it was initially known as reduces Egr1 promoter activity . Transcriptional co-
[4]
[1]
nerve growth factor inducible protein A (NGFI-A) . Egr1 repressors NGFI-A binding protein 1 and 2 (NAB1
is one of four family members that also include Egr2, and NAB2, respectively) repress Egr1, Egr2, and Egr3
Egr3, and Egr4 . Also known as Krox24, zif268, and transcriptional activity by binding to the respective
[2]
TIS8, Egr1 encodes a protein of 80-82 kDa that consists repressor domains upstream of the zinc finger motifs
of three zinc finger DNA-binding motifs [Figure 1]. Thus, and could potentially co-regulate Egr1 target genes [5-7] .
Quick Response Code:
This is an open access article licensed under the terms of Creative Commons Attribution 4.0 International
License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution,
and reproduction in any medium, as long as the original author is credited and the new creations are licensed under the
identical terms.
For reprints contact: service@oaepublish.com

268 © The author(s) 2017 www.oaepublish.com