NDRG1 protein; differentiation-related gene 1 protein; DRG-1; N-myc downstream-regulated gene 1 protein; nickel-specific induction protein Cap43; reducing agents & tunicamycin-responsive protein; RTP; Rit42 (NDRG1, CAP43, DRG1, RTP)

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Function

stress-responsive protein involved in hormone responses, cell growth, & differentiation
acts as a tumor suppressor protein in many cell types
necessary but not sufficient for p53/TP53-mediated caspase activation & apoptosis.
role in cell trafficking, notably of the Schwann cell
- necessary for maintenance & development of the peripheral nerve myelin sheath
required for vesicular recycling of CDH1 & TF
may also function in lipid trafficking
protects cells from spindle disruption damage
functions in p53/TP53-dependent mitotic spindle checkpoint
regulates microtubule dynamics & maintains euploidy
under stress conditions, phosphorylated in the C-terminal on many Ser & Thr
phosphorylated in vitro by PKA
phosphorylation enhanced by increased intracellular cAMP levels
homocysteine induces dephosphorylation
phosphorylation by SGK1 is cell cycle dependent
interacts with RAB4A (membrane-bound form)
- the interaction involves NDRG1 in vesicular recycling of CDH1

belongs to the NDRG family

cytoplasm, cytoskeleton,
centrosome, nucleus, cell membrane
mainly cytoplasmic but differentially localized to other cell regions
associates with the plasma membrane in intestinal epithelia & lactating mammary gland
translocated to the nucleus in a p53/TP53-dependent manner
in prostate epithelium & placental chorion, located in both cytoplasm & in the nucleus
no nuclear localization in colon epithelium cells
in intestinal mucosa, prostate & renal cortex, located predominantly adjacent to adherens junctions
cytoplasmic with granular staining in proximal tubular cells of the kidney & salivary gland ducts
recruited to the membrane of recycling/sorting & late endosomes via binding to phosphatidylinositol 4-phosphate
associates with microtubules
colocalizes with TUBG1 in the centrosome
cytoplasmic location increased with hypoxia
phosphorylated form found associated with centromeres during S-phase of mitosis & with the plasma membrane

ubiquitously expressed
expressed most prominently in placental membranes & prostate, kidney, small intestine, & ovary tissues
also expressed in heart, brain, skeletal muscle, lung, liver & pancreas
low levels in peripheral blood leukocytes & in tissues of the immune system
expressed mainly in epithelial cells
also found in Schwann cells of peripheral neurons
reduced expression in adenocarcinomas compared to normal tissues
in colon, prostate & placental membranes, the cells that border the lumen show the highest expression
induced by homocysteine, 2-mercaptoethanol, tunicamycin in endothelial cells
induced approximately 20-fold during in vitro differentiation of the colon carcinoma cell lines HT29-D4 & Caco-2
induced by oxidative stress in colon cancers
decreased expression in colon adenomas & adenocarcinomas
induced by nickel compounds in all tested cell lines
- the primary signal for its induction is an elevation of free intracellular Ca+2 caused by nickel ion exposure
- okadaic acid, a serine/threonine phosphatase inhibitor, induces its expression more rapidly & more efficiently than nickel