NDRG3 Human

N-Myc Downstream Regulated 3 (NDRG3) is a member of the N-Myc Downstream Regulated Gene (NDRG) family, which is part of the larger α/β-hydrolase superfamily . The NDRG family includes four members: NDRG1, NDRG2, NDRG3, and NDRG4, each playing distinct roles in cellular processes such as proliferation, differentiation, and stress responses .

The NDRG3 gene is located on chromosome 20q11.21 and encodes a protein that is approximately 41 kDa in size . The protein structure of NDRG3 adopts the α/β-hydrolase fold, which is characterized by eight canonical β-strands surrounded by α-helices . Despite its structural similarity to other hydrolases, NDRG3 lacks enzymatic activity due to the substitution of key catalytic residues .

NDRG3 expression is regulated by the MYC oncogene, specifically N-Myc, which is known to repress the expression of NDRG family members . NDRG3 is expressed in various tissues, with notable expression in the prostate, liver, and brain . During embryonic development, NDRG3 expression is observed as early as embryonic day 9.5 (E9.5) .

NDRG3 plays a crucial role in several physiological processes:

• Cell Proliferation and Differentiation: NDRG3 is involved in the regulation of cell proliferation and differentiation, particularly in prostate cancer cells .
• Hypoxia Response: NDRG3 has been implicated in hypoxia-induced cancer metabolism, where it responds to lactate levels and contributes to tumorigenesis .
• Oncogenic Progression: The flexible loop region of NDRG3, which differs from other NDRG family members, is believed to play a distinct role in oncogenic progression .

Given its involvement in cancer metabolism and tumor progression, NDRG3 is a potential target for therapeutic interventions. Understanding the structural and functional characteristics of NDRG3 can aid in the development of targeted therapies for cancers where NDRG3 plays a significant role .