Abstract
The protein N-Myc downstream-regulated gene 1 (NDRG1) is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV) light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER) and microtubules. Mutation of the phosphopantetheine attachment site (PPAS) within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1’s subcellular distribution.
Highlights
N-Myc downstream-regulated gene 1 (NDRG1) is a 394-amino acid protein that is implicated in cell differentiation, stress, and hormonal response [1,2,3,4,5,6,7,8]
We initially determined that the expression of NDRG1 protein in the trophoblast cell lines JEG-3, BeWo, and HTR-8/SVneo was markedly higher than other non-placental cell types, such as the myometrial line SHM, the ovarian line CHO, and NIH3T3 fibroblasts (Figure 1A)
Building upon our previous data on the expression and anti-apoptotic function of NDRG1 in trophoblasts exposed to hypoxia [16,17,48], we showed that the expression of NDRG1 is not upregulated by any cell stressor, but is selectively enhanced by hypoxia or hypoxia mimetic chemicals
Summary
NDRG1 ( called RTP, DRG1, CAP43, RIT42, TDD5, NDR1, and PROXY1) is a 394-amino acid protein that is implicated in cell differentiation, stress, and hormonal response [1,2,3,4,5,6,7,8]. The expression of NDRG1 in murine Schwann cells is enhanced during regeneration after sciatic nerve injury [11] These findings are attributed to a stop codon non-sense mutation (R148X) [12] or to an exon-9-skipping mutation (IVS8-1G>A, S181-K198) [13] found in humans with hereditary motor and sensory neuropathy-Lom (HMSNL, known as Charcot-Marie-Tooth type 4D disease). This disease is characterized by Schwann cell demyelination and concomitant early axonal impairment affecting both motor and sense peripheral nerves, and resulting in a loss of limb muscle function and touch sensation in adulthood [12,13]. NDRG1-null mice exhibit impaired mast cell differentiation and degranulation [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
