The N‐myc downstream regulated gene (NDRG) family: diverse functions, multiple applications

Abstract

The N-myc downstream regulated gene (NDRG) family of proteins consists of 4 members, NDRG1-4, which are well conserved through evolution. The first member to be discovered and responsible for the family name was NDRG1, because its expression is repressed by the proto-oncogenes MYCN and MYC. All family members are characterized by an α/β hydrolase-fold motif; however, the precise molecular and cellular function of these family members has not been fully elucidated. Although the exact function of NDRG family members has not been clearly elucidated, emerging evidence suggests that mutations in these genes are associated with diverse neurological and electrophysiological syndromes. In addition, aberrant expression as well as tumor suppressor and oncogenic functions affecting key hallmarks of carcinogenesis such as cell proliferation, differentiation, migration, invasion, and stress response have been reported for several of the NDRG proteins. In this review, we summarize the current literature on the NDRG family members concerning their structure, origin, and tissue distribution. In addition, we review the current knowledge regarding the regulation and signaling of the NDRG family members in development and normal physiology. Finally, their role in disease and potential clinical applications (their role as detection or prognostic markers) are discussed.

NDRG4 Protein-deficient Mice Exhibit Spatial Learning Deficits and Vulnerabilities to Cerebral Ischemia

“…Furthermore, accumulating evidence implicates their roles in development, cancer metastasis, and the immune system (1)(2)(3)(4)(5).…”

Methylthioadenosine (MTA) Regulates Liver Cells Proteome and Methylproteome: Implications in Liver Biology and Disease

“…2A). Decreased expression of NDRG1 in SK-Hep1 cells might also be associated with their differentiation state (43). APEX1 and TGM2 are increased when MTA accumulates and may modulate apoptosis and provide drug resistance (44).…”

“…PGK1 participates in angiostatin synthesis and release, a potent inhibitor of angiogenesis and tumoral growth (42). NDRG1 is an N-myc down-regulated protein that is considered a tumor suppressor with the capacity to revert metastatic processes (43). In addition to its capacity to regulate cell growth, PRDX3 might be also providing drug resistance mechanisms in cancer cells (59) as its activity scavenges reactive oxygen species mitigating the apoptotic effects of chemotherapy (60).…”

Regulation of N-Myc downstream regulated gene 2 by bile acids

“…N-myc downstream-regulated gene 2 (NDRG2) belongs to the NDRG family, comprised of four members, NDRG1-4, which are reportedly involved in cell proliferation and differentiation [1,2]. NDRG2 is highly expressed in many normal tissues, especially in the brain, heart, skeletal muscle, liver, and kidney, whereas low expressed or undetectable in a variety of human cancer cell lines and carcinomas [1,2].…”

“…NDRG2 is highly expressed in many normal tissues, especially in the brain, heart, skeletal muscle, liver, and kidney, whereas low expressed or undetectable in a variety of human cancer cell lines and carcinomas [1,2]. Recently, NDRG2 was identified as a novel tumor metastasis suppressor in hepatocellular carcinoma (HCC) [3].…”