NDRG2

Official Full Name

NDRG family member 2

Organism

Homo sapiens

GeneID

57447

Background

This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that may play a role in neurite outgrowth. This gene may be involved in glioblastoma carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

Synonyms

SYLD;

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Detailed Information

NDRG2 belongs to the NDRG family (N-myc down-stream regulated gene family) and is a tumor suppressor gene related to cell proliferation and differentiation. It is widely distributed and has complex biological functions. It is expressed in various tissues and organs throughout the body. NDRG2 is involved in tissue embryo development, cell differentiation and is closely related to the blood immune system. It protects tissues from ischemia-reperfusion injury and is closely related to the occurrence, development and outcome of tumors.

Structural and Biological Characteristics of NDRG2

The NDRG2 gene chromosome is located at 14q11. 2, contains 16 exons, 15 introns. Human NDRG2 mRNA was cloned in a normal adult whole brain cDNA library and was 2024 bp in length. In humans, NDRG2 contains an APC-like domain and is a unique domain of the NDRG family, regulated by the expression of the proto-oncogene N - Myc. It has been found that NDRG2 has two different transcriptional regulators in humans, and a tiny promoter may exist between the two transcriptional initiation sites. The NDRG2 homologous protein is only found in the metaplastic layer and does not exist in the prokaryotic layer. These homologous proteins are involved in cell differentiation.

NDRG2 is involved in tissue embryo development. The NDRG2 protein is not a tissue-specific protein. It is involved in the formation of myocardium, fetal lung, fetal liver, renal tubules, small intestinal villus epithelial cells, colonic epithelial cells, skin surface cells and hair follicles and thymus bodies. In embryonic tissues, the expression of NDRG2 is increased with the prolongation of embryonic age, but the expression levels of NDRG2 mRNA and protein are not consistent. For example, in fetal liver, NDRG2 mRNA expression is low and protein expression is high, and fetal kidney is opposite. The expression of NDRG2 mRNA and protein in different organs is inconsistent, indicating that the gene expression regulation is diverse.

Figure 1. Processes targeted by NDRG2. (Hu, W., et al. 2016)

NDRG2 and the Blood Immune System

NDRG2 is closely related to the blood immune system. The study found that NDRG2 protein is highly expressed in DCs in DC cells (including monocyte and DC cell-derived monocytic leukemia cells), in vivo lymph nodes, thymus, and skin. In addition, 14 insertion sequences have been found in the cytoplasm. It is pointed out that the interference of NDRG2 expression can induce the down-regulation of activated leukocyte adhesion molecule (ALCAM). Overexpression of NDRG2 can prevent the induction of ALCAM cytokines in monocyte cell lines. Down-regulation of NDRG2 can reduce the proliferation of DC-stimulated allogeneic T cells. The ability to consider the expression of NDRG2 in DCs may be the ability to maintain T lymphocyte stimulating activity by continually stimulating molecular expression.

In astrocytes, NDRG2 signaling occurs from cytoplasmic translocation to nuclear localization after 24 hours of reperfusion, suggesting that NDRG2 expression in astrocytes may play an important pathological role in post-stroke apoptosis. In a more in-depth study, insulin inhibits cardiomyocyte apoptosis and reduces myocardial infarct size during myocardial ischemia-reperfusion, significantly upregulating phosphorylation of Akt and NDRG2 in the myocardium. In addition, down-regulation of NDRG2 by shRNA significantly aggravated myocardial ischemia-reperfusion injury (IRI) and inhibited insulin-mediated IRI protection, and NDRG2/PIK3/AKT was identified as a transmitter involved in signaling.

References:

Hu, W. , Fan, C. , Jiang, P. , Ma, Z. , Yan, X. , & Di, S. , et al. (2016). Emerging role of n-myc downstream-regulated gene 2 (ndrg2) in cancer. Oncotarget, 7(1), 209-223.
Xi’an Li, Hou, G. , Zhu, Z. , Yan, F. , Wang, F. , & Wei, D. , et al. (2019). The tumor suppressor ndrg2 cooperates with an mtorc1 inhibitor to suppress the warburg effect in renal cell carcinoma.
Ichikawa, T., Nakahata, S., Fujii, M., Iha, H., & Morishita, K. (2015). Loss of ndrg2 enhanced activation of the nf-κb pathway by pten and nik phosphorylation for atl and other cancer development. Scientific Reports, 5(1), 12841.

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