Affinage

NDRG1

Protein NDRG1 · UniProt Q92597

Round 2 corrected
Length
394 aa
Mass
42.8 kDa
Annotated
2026-04-29
130 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NDRG1 is a stress-responsive, non-catalytic alpha/beta hydrolase-fold protein that functions as a scaffold integrating signal transduction, vesicular trafficking, and organelle homeostasis in response to iron depletion, hypoxia, and other cellular stresses. Its C-terminal GTRSRSHTSE decapeptide repeats are sequentially phosphorylated by mTORC2–SGK1 (Thr328/330/346/356/366) and then GSK3 (Ser342/352/362), and mTORC2-dependent phosphorylation at Ser336 directs NDRG1 to mitochondria where it cooperates with CDC42 to drive DRP1-independent mitochondrial fission (PMID:15461589, PMID:37386153). NDRG1 suppresses metastasis by inhibiting EGFR/HER2/HER3 heterodimerization and downstream receptor tyrosine kinase signaling, regulates endosomal LDLR trafficking through multivesicular body formation, maintains centrosome homeostasis via γ-tubulin interaction downstream of p53, and prevents ATG9A-dependent autophagic degradation of MHC-I to sustain anti-tumor immunity (PMID:28615452, PMID:23813961, PMID:26324937, PMID:38228036). Loss-of-function mutations in NDRG1 cause CMT4D (hereditary motor and sensory neuropathy-Lom), a demyelinating neuropathy attributable to impaired Schwann cell vesicular trafficking (PMID:10831399, PMID:21303696).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1996 Medium

    The initial identification of NDRG1 as a stress-responsive cytoplasmic protein induced by homocysteine, ER stress agents, and reducing conditions established it as a gene whose expression reports on cellular stress, but its function remained unknown.

    Evidence Differential display and Northern blot cloning from HUVECs treated with homocysteine, tunicamycin, and 2-mercaptoethanol

    PMID:8939898

    Open questions at the time
    • No function assigned beyond stress responsiveness
    • Protein localization at the subcellular level not determined
    • Mechanism of transcriptional induction not identified
  2. 2000 High

    Positional cloning of NDRG1 as the causative gene for CMT4D (HMSNL) and its concurrent identification as a metastasis suppressor in colon cancer established two cardinal biological roles — peripheral nerve maintenance and tumor suppression — raising the question of what molecular function could unify them.

    Evidence Positional cloning and mutation analysis in HMSNL families; stable overexpression in SW620 cells with in vivo liver metastasis assay in nude mice

    PMID:10676663 PMID:10831399

    Open questions at the time
    • Molecular mechanism of metastasis suppression unknown
    • How a cytoplasmic protein maintains Schwann cell myelination not addressed
    • Whether the two phenotypes share a common pathway unclear
  3. 2001 High

    Biophysical characterization of the C-terminal TRSRSHTSEG repeats revealed direct metal ion (Ni²⁺, Cu²⁺) coordination through histidine imidazole and deprotonated backbone amides, providing a structural basis for nickel-dependent induction and suggesting the repeat region serves as both a regulatory phosphorylation target and a metal-binding module.

    Evidence pH-metric titration, UV-VIS, EPR, CD, and NMR spectroscopy with synthetic decapeptide repeats

    PMID:11330481

    Open questions at the time
    • Physiological relevance of metal binding in vivo not established
    • Whether metal binding competes with phosphorylation not tested
  4. 2004 High

    Identification of SGK1 as the kinase that phosphorylates NDRG1 at five threonine sites, priming subsequent GSK3 phosphorylation at three serine sites, placed NDRG1 squarely downstream of the PI3K–mTORC2–SGK1 axis and defined the first signaling pathway controlling its post-translational modification.

    Evidence In vitro kinase assays with mass spectrometry site identification, validated in SGK1-knockout mouse tissues, siRNA, and GSK3 inhibitor in cells

    PMID:15461589

    Open questions at the time
    • Functional consequence of SGK1/GSK3 phosphorylation on NDRG1 activity not determined
    • Whether other kinases act on these sites in specific tissues unknown
  5. 2004 High

    Demonstration that iron chelation upregulates NDRG1 through both HIF-1α-dependent and -independent pathways, reversible by iron repletion, revealed iron as a master regulator of NDRG1 expression and connected NDRG1 to hypoxia and iron-metabolism signaling.

    Evidence Multiple iron chelators with inactive-binding-site controls, iron repletion, Northern/Western blot, and HIF-1α pathway dissection

    PMID:15251988

    Open questions at the time
    • Direct transcription factor binding to NDRG1 promoter under iron depletion not mapped
    • Relative contribution of HIF-1α-dependent vs -independent pathways unresolved
  6. 2004 Medium

    Localization of NDRG1 to centrosomes and its requirement for proper spindle formation and astral microtubule maintenance linked NDRG1 to mitotic fidelity and the p53-dependent spindle checkpoint, offering the first mechanistic connection between NDRG1 and genomic stability.

    Evidence Immunofluorescence centrosome localization, siRNA knockdown causing spindle defects, overexpression restoring spindle-checkpoint arrest in p53-null cells

    PMID:15247272

    Open questions at the time
    • Direct binding partner at centrosomes not identified at this stage
    • Whether centrosome role accounts for metastasis suppression unclear
  7. 2013 High

    Two studies established NDRG1 as a regulator of receptor trafficking and a stabilizer of DNA-repair protein MGMT: NDRG1 controls LDLR endosomal sorting by opposing IDOL-mediated ubiquitylation and multivesicular body targeting, while NDRG1–MGMT interaction confers alkylating-agent resistance in glioblastoma, demonstrating that NDRG1 functions through specific protein–protein interactions rather than enzymatic activity.

    Evidence siRNA epistasis (NDRG1/IDOL co-depletion) with LDLR plasma-membrane and ubiquitylation readouts; Co-IP of NDRG1–MGMT with functional drug-resistance assays

    PMID:23813961 PMID:24367102

    Open questions at the time
    • Structural basis of NDRG1–MGMT and NDRG1–LDLR/ESCRT interactions not resolved
    • Whether LDLR trafficking role extends to other cargo receptors unknown
  8. 2015 High

    Identification of γ-tubulin as a direct NDRG1 binding partner resolved the centrosomal mechanism: NDRG1 maintains centrosome homeostasis downstream of p53, and its loss causes centrosome amplification, explaining NDRG1's role in genomic stability and mutual exclusivity with TP53 loss in cancers.

    Evidence Co-immunoprecipitation of NDRG1–γ-tubulin, RNAi and overexpression with centrosome counting, isogenic TP53 cell lines, cancer genomics

    PMID:26324937

    Open questions at the time
    • Domain on NDRG1 mediating γ-tubulin binding not mapped
    • Whether phosphorylation state modulates centrosome engagement unknown
  9. 2015 High

    Discovery that NDRG1 is a T-cell clonal anergy factor induced by Egr2, degraded via phosphorylation and proteasome upon CD28/IL-2 signaling, expanded NDRG1's role beyond epithelial biology into adaptive immunity.

    Evidence Ndrg1 overexpression, conditional knockout mice, proteasome inhibitor treatment, T-cell anergy models

    PMID:26507712

    Open questions at the time
    • Kinase responsible for CD28-triggered NDRG1 phosphorylation not identified
    • Whether NDRG1's trafficking function underpins anergy mechanism unknown
  10. 2022 High

    NDRG1 was shown to bind Nur77 and NF-κB to regulate endothelial inflammatory signaling; endothelial-specific NDRG1 knockout attenuated atherosclerosis, neointima formation, and arterial thrombosis, establishing NDRG1 as a pro-inflammatory mediator in endothelial cells — a role distinct from its tumor-suppressive function in epithelia.

    Evidence Co-IP of NDRG1–Nur77, endothelial-specific conditional knockout mice, carotid ligation and thrombosis models, luciferase reporters for NF-κB and AP-1

    PMID:36562299

    Open questions at the time
    • Whether endothelial NDRG1 acts through the same trafficking mechanism as in epithelia not tested
    • Structural basis of NDRG1–Nur77 interaction unknown
  11. 2023 High

    Identification of mTORC2-mediated Ser336 phosphorylation as a signal that directs NDRG1 to mitochondria to drive DRP1-independent fission through cooperation with CDC42 provided the first direct organellar effector mechanism for phospho-NDRG1, linking nutrient sensing to mitochondrial dynamics.

    Evidence Live imaging, phospho-Ser336-specific antibodies, Rictor-KO and NDRG1-S336A epistasis, DRP1-KO cells, proteomics

    PMID:37386153

    Open questions at the time
    • Structural basis of NDRG1–CDC42 cooperation at the mitochondrial surface not resolved
    • Whether this fission mechanism operates in Schwann cells relevant to CMT4D unknown
  12. 2024 Medium

    NDRG1 was found to prevent ATG9A-dependent autophagy-mediated degradation of MHC-I in pancreatic cancer, restoring antigen presentation and overcoming immune checkpoint blockade resistance, extending NDRG1's trafficking role to autophagy-mediated surface receptor regulation and anti-tumor immunity.

    Evidence Co-IP of NDRG1–ATG9A, orthotopic PDAC models, autophagy/proteasome inhibitors, flow cytometry for CD8⁺ T cells

    PMID:38228036

    Open questions at the time
    • Whether NDRG1 broadly opposes selective autophagy of membrane receptors beyond MHC-I not tested
    • Direct interaction domain mapping not performed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The unifying structural basis for NDRG1's diverse protein–protein interactions (γ-tubulin, MGMT, Nur77, ATG9A, AR-HSP90, CDC42) remains unresolved: no high-resolution structure of full-length NDRG1 or its complexes exists, and how its alpha/beta hydrolase fold, CAP domain, and C-terminal repeat region coordinately engage different partners in different cellular contexts is the central open question.
  • No crystal or cryo-EM structure of full-length NDRG1 or any of its complexes
  • How phosphorylation switches partner specificity is mechanistically undefined
  • Whether NDRG1's role in Schwann cell trafficking and its mitochondrial fission function share a common membrane-remodeling mechanism is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005815 microtubule organizing center 3 GO:0005829 cytosol 2 GO:0005739 mitochondrion 1 GO:0005768 endosome 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2 R-HSA-382551 Transport of small molecules 2 R-HSA-5653656 Vesicle-mediated transport 1 R-HSA-9612973 Autophagy 1
Partners
ARATG9ACDC42GSK3BMGMTNR4A1SGK1TUBG1

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 Cap43 (NDRG1) mRNA is specifically induced by nickel compounds (Ni3S2 or NiCl2) via elevation of free intracellular Ca2+, as demonstrated by induction with calcium ionophores and attenuation by intracellular Ca2+ chelation; induction is not mimicked by oxidative stress or heat shock, and okadaic acid (a serine/threonine phosphatase inhibitor) induces Cap43 more strongly than nickel, implicating phosphatase-regulated signaling in its regulation. mRNA differential display, calcium ionophore treatment, intracellular Ca2+ chelation with BAPTA-AM, okadaic acid treatment, Northern blot in human and rodent cells Cancer research Medium 9605764
1999 Ndrg1 is transcriptionally repressed by N-myc: N-myc (and c-myc) together with Max down-regulate the Ndrg1 promoter through a region within 52 bp of the transcription start site, and this repression requires histone deacetylase activity (sensitive to Trichostatin A); direct binding of N-myc:Max to the promoter was not demonstrated, analogous to indirect repression mechanisms reported for c-myc targets. Promoter-reporter cotransfection assay, Trichostatin A treatment, whole-embryo cDNA subtraction in N-myc-deficient mice, in situ hybridization Mechanisms of development Medium 10381566
1996 NDRG1 (originally named RTP) was first identified as a homocysteine-responsive gene product in vascular endothelial cells, also induced by 2-mercaptoethanol and tunicamycin (ER stress inducers), establishing it as a stress-responsive cytoplasmic protein. Differential display, Northern blot, full-length cDNA cloning from HUVEC library The Journal of biological chemistry Medium 8939898
2000 NDRG1 is phosphorylated by protein kinase A (PKA) at multiple sites (seven or more) in vitro and in cells; phosphorylation is reversible, enhanced by elevated intracellular cAMP, inhibited by a PKA inhibitor and a calmodulin kinase inhibitor, and is more abundant in cells at early log phase. Western blot (phosphorylation state), in vitro PKA phosphorylation of recombinant RTP/NDRG1, PKA inhibitor treatment, cAMP elevation, calmodulin kinase inhibitor Biochemical and biophysical research communications Medium 10860807
2000 Mutations in NDRG1 (premature termination codon at position 148) cause hereditary motor and sensory neuropathy-Lom (HMSNL/CMT4D); NDRG1 is expressed at particularly high levels in Schwann cells, implicating it in Schwann-cell signaling necessary for axonal survival. Positional cloning, genomic sequencing, mutation analysis, in situ hybridization and immunohistochemistry in peripheral nerve American journal of human genetics High 10831399
2000 Drg-1/NDRG1 overexpression in metastatic colon cancer cells (SW620) induced morphological differentiation, up-regulated differentiation markers (alkaline phosphatase, CEA, E-cadherin), reduced in vitro Matrigel invasion, and suppressed in vivo liver metastases in nude mice, establishing it as a metastasis suppressor. Stable transfection, Matrigel invasion assay, nude mouse liver metastasis model, Western blot, differentiation marker assays Cancer research High 10676663
2001 The C-terminal TRSRSHTSEG repeat region of Cap43/NDRG1 protein coordinates Ni(II) and Cu(II) ions; each 10-amino acid histidine-containing repeat independently binds one metal ion, forming square-planar 4N complexes at physiological-to-alkaline pH involving the imidazole nitrogen of histidine and three deprotonated backbone amide nitrogens. pH-metric titration, UV-VIS, EPR, CD, NMR spectroscopy with synthetic peptides modeling the Cap43 C-terminus Journal of inorganic biochemistry High 11330481
2002 NDRG1 protein localizes primarily to the cytoplasm in epithelial cells and is also associated with the cellular membrane and adherens junctions; electron microscopy confirmed association with the E-cadherin/catenin complex, suggesting a functional role in cell-cell adhesion. Immunohistochemistry (light and electron microscopy) on normal human tissues, subcellular localization Histochemistry and cell biology Medium 12432451
2003 VHL tumor suppressor specifically down-regulates Cap43/NDRG1 expression in renal cancer cells; promoter deletion analysis identified an Sp1 site in the -286 to -62 bp region as partly responsible for VHL-induced suppression, and Cap43 mRNA remains inducible by hypoxia or nickel only in VHL-positive cell lines. VHL transfection into 786-O cells, Cap43 promoter deletion/mutation reporter assays, Northern blot, immunostaining International journal of cancer Medium 12767066
2003 Xenopus NDRG1 (xNDRG1) is required for pronephros development; morpholino-mediated depletion causes failure of pronephros development, and overexpression results in a reduced pronephros and disorganized somites, demonstrating a conserved developmental role. Morpholino antisense knockdown, mRNA overexpression, whole-mount in situ hybridization in Xenopus laevis embryos Biochemical and biophysical research communications Medium 12943662
2003 The cellular distribution of NDRG1 protein changes during postnatal development in rat kidney (from proximal convoluted tubules to collecting ducts) and brain (from hippocampal pyramidal neurons to astrocytes) between postnatal days 10–20; concomitantly, NDRG1 shifts from a high-molecular-weight complex (~215 kDa under non-reducing conditions) to monomeric forms, suggesting developmental regulation of its assembly state. Immunohistochemistry, Western blot under reducing and non-reducing conditions across postnatal time points in rat The journal of histochemistry and cytochemistry Medium 14566023
2004 SGK1 phosphorylates NDRG1 at Thr328, Ser330, Thr346, Thr356, and Thr366 in vitro; these phosphorylations occur in vivo in multiple tissues of wild-type but not SGK1-knockout mice. SGK1-mediated phosphorylation of NDRG1 at Thr346 primes it for subsequent phosphorylation by GSK3 at Ser342, Ser352, and Ser362 in the GTRSRSHTSE decapeptide repeat region; GSK3 inhibition increases NDRG1 electrophoretic mobility in cells. In vitro kinase assays (SGK1, GSK3), mass spectrometry of phosphorylation sites, SGK1-knockout mouse tissues, siRNA knockdown of SGK1 in HeLa cells, GSK3 inhibitor CT99021 The Biochemical journal High 15461589
2004 Iron chelation specifically up-regulates NDRG1 mRNA and protein expression through iron depletion; this induction is reversed by iron repletion, requires the iron-binding activity of the chelators (inactivated-binding-site chelator had no effect), correlates with their antiproliferative activity, and occurs via both HIF-1α-dependent and HIF-1α-independent transcriptional mechanisms. Gene array, Northern blot, Western blot, iron repletion experiments, HIF-1α pathway analysis, chelator Fe-complex controls Blood High 15251988
2004 Drg1/Rit42 (NDRG1) localizes to centrosomes and is a microtubule-associated protein; ectopic expression in p53-deficient tumor cells inhibited spindle-inhibitor-induced polyploidy and increased mitotic arrest, while siRNA knockdown in normal mammary epithelial cells caused disappearance of astral microtubules, defective spindle formation, and microtubule inhibitor-induced reduplication leading to polyploidy, establishing NDRG1 as a participant in the p53-dependent spindle checkpoint. Immunofluorescence/centrosome localization, ectopic expression, siRNA knockdown, flow cytometry (ploidy), spindle inhibitor treatment The Journal of biological chemistry Medium 15247272
2004 NDRG1 (Drg1) is markedly upregulated (~14-fold) by androgens in LNCaP prostate cancer cells; this induction reflects the altered specificity of the mutated androgen receptor in LNCaP cells and is absent in androgen receptor-negative tumor lines, identifying NDRG1 as an androgen-responsive gene. Differential display, Northern blot, androgen treatment, androgen receptor-negative cell line controls FEBS letters Medium 10428464
2006 Cap43/NDRG1 overexpression in pancreatic cancer cells did not alter in vitro growth but markedly suppressed in vivo tumor growth by reducing tumor-induced angiogenesis; mechanistically, Cap43 overexpression decreased expression of MMP-9, VEGF, and IL-8, and reduced gelatinolytic/invasive activity. Stable transfection, xenograft tumor growth, Matrigel invasion, gelatin zymography, Western blot for MMP-9/VEGF/IL-8 Cancer research Medium 16778198
2009 Ndrg1 is a T-cell clonal anergy factor induced by Egr2: Ndrg1 overexpression mimics the anergic state, and knockout prevents anergy induction; Ndrg1 is phosphorylated and degraded via the proteasome upon CD28 co-stimulation, explaining why co-stimulation prevents anergy; IL-2 treatment of anergic T cells similarly induces Ndrg1 phosphorylation and degradation, reversing anergy. Overexpression, conditional knockout (Ndrg1-KO mice), proteasome inhibitor treatment, phosphorylation assays, T-cell anergy induction models, autoimmune inflammation assay Nature communications High 26507712
2011 NDRG1 phosphorylation by SGK1 is temporally and spatially controlled during the cell cycle: phosphorylated NDRG1 co-localizes with γ-tubulin at centromeres and at the cleavage furrow during cytokinesis; p53 deficiency increases basal NDRG1 expression and SGK1-mediated phosphorylation. Immunofluorescence co-localization with γ-tubulin, cell cycle synchronization (aphidicolin/nocodazole), Western blot in p53-proficient and -deficient HCT116 cells Biochemical and biophysical research communications Medium 21708134
2011 Total Ndrg1 deficiency in the stretcher mouse model causes demyelinating neuropathy with onset between postnatal weeks 3 and 5 coinciding with rapid myelin growth; even low-level Ndrg1 expression provides significant phenotypic rescue; impaired Schwann cell trafficking (not growth arrest, differentiation, or proteasomal dysfunction) emerges as the likely pathogenic mechanism. Ndrg1-null (stretcher) and hypomorphic knockout mouse characterization, morphological/histological analysis, gene expression profiling, proteasomal function assays Neurobiology of disease Medium 21303696
2013 NDRG1 silencing in epithelial cells reduces LDL receptor (LDLR) abundance at the plasma membrane by causing LDLR accumulation in enlarged EEA1-positive endosomes with increased LDLR ubiquitylation; co-depletion of IDOL (the E3 ligase that ubiquitylates LDLR) rescues plasma membrane LDLR and LDL uptake. In murine oligodendrocytes, Ndrg1 silencing reduces LDL uptake and downregulates Olig2, both rescued by Idol co-silencing. This establishes NDRG1 as a regulator of multivesicular body formation and endosomal LDLR trafficking. siRNA knockdown, co-depletion epistasis, immunofluorescence (EEA1/LDLR co-localization), LDL uptake assay, ubiquitylation assay, ESCRT protein Western blot Journal of cell science High 23813961
2013 NDRG1 binds and stabilizes MGMT (O6-methylguanine-DNA methyltransferase) protein; this interaction confers MGMT-dependent resistance to alkylating chemotherapy in glioblastoma, driven by hypoxia, irradiation, corticosteroids, and chronic alkylating agent exposure via HIF-1α, p53, and mTORC2/SGK1 pathways. Co-immunoprecipitation (NDRG1-MGMT interaction), NDRG1 siRNA knockdown, mTOR pathway inhibition, posttreatment tumor tissue analysis, drug resistance assays Proceedings of the National Academy of Sciences of the United States of America High 24367102
2015 NDRG1 physically associates with γ-tubulin (a key centrosome component) and mediates centrosome homeostasis downstream of p53: NDRG1 expression is induced by p53 under physiologic low-proliferative conditions, and loss of NDRG1 (by RNAi) causes centrosome amplification; TP53 null cells fail to increase NDRG1 and show aberrant centrosome numbers. TP53 homozygous loss was mutually exclusive with NDRG1 overexpression in >96% of human cancers. Co-immunoprecipitation (NDRG1-γ-tubulin), RNAi knockdown, overexpression, centrosome counting, isogenic TP53 wild-type/null/R248W cell lines, cancer genomics analysis Proceedings of the National Academy of Sciences of the United States of America High 26324937
2015 SUMO-2 modification of NDRG1 at Lys14 regulates its protein stability: a SUMO-2-fused NDRG1 K14R mutant shows dramatically decreased protein stability compared to wild-type or the K14R SUMO-acceptor mutant alone; SUMO-2 modification does not affect NDRG1 subcellular distribution but reduces p21 expression when fused SUMO-2 NDRG1 K14R is overexpressed. SUMO modification assay, site-directed mutagenesis (K14R), stability assays, subcellular fractionation, Western blot for p21 Biochemical and biophysical research communications Medium 25712528
2016 NDRG1 physically associates with TLE2 and β-catenin to activate the Wnt/β-catenin pathway in esophageal squamous cell carcinoma cells; NDRG1 overexpression decreases TLE2 expression and increases β-catenin, inducing EMT; RNAi-mediated knockdown of TLE2 phenocopied NDRG1 overexpression, while TLE2 overexpression blocked NDRG1-mediated Wnt activation. Co-immunoprecipitation (NDRG1-TLE2, NDRG1-β-catenin), stable lentiviral overexpression, RNAi, Western blot for EMT markers Cancer biology & therapy Medium 27414086
2017 NDRG1 inhibits EGFR/HER2 heterodimer and HER2/HER3 heterodimer formation, and promotes EGFR degradation; iron depletion (via novel thiosemicarbazone chelators) increases NDRG1 expression which in turn attenuates ErbB receptor signaling. Co-immunoprecipitation (EGFR/HER2, HER2/HER3 dimerization), NDRG1 overexpression/knockdown, receptor degradation assays, iron chelator treatment The Journal of biological chemistry Medium 28615452
2017 SGK1-mediated phosphorylation of Ndrg1 is induced during adipogenesis and promotes adipocyte differentiation and function by inducing PPARγ expression; Ndrg1 is also required for C/EBPα phosphorylation during adipogenesis; mTORC2 activation (via SGK1) is upstream of Ndrg1 phosphorylation in this context. siRNA knockdown, overexpression, adipogenesis assays, Western blot (PPARγ, C/EBPα phosphorylation), mTORC2 inhibitor treatment Scientific reports Medium 28775290
2019 NDRG1 modulates the three arms of the ER stress response: it increases expression of ER chaperones BiP, calreticulin, and calnexin; suppresses PERK; inhibits IRE1α; and increases cleavage of ATF6. In the presence of Dp44mT (an iron chelator that up-regulates NDRG1), NDRG1 markedly increases eIF2α activation, maintains ATF4 expression, elevates cytosolic Ca2+, activates CaMKII, and increases pro-apoptotic CHOP. NDRG1 overexpression/siRNA knockdown, Western blot for ER stress pathway components, Ca2+ measurement, Dp44mT treatment, anti-proliferation/migration assays Biochimica et biophysica acta. Molecular basis of disease Medium 30981813
2019 NDRG1 and GSK3β form a bidirectional regulatory loop in glioblastoma: NDRG1 overexpression promotes proteasomal degradation of GSK3β, suppressing AKT/S6 and cell-cycle signaling; conversely, GSK3β phosphorylates serine and threonine residues in the C-terminal domain of NDRG1, limiting NDRG1 protein stability. NDRG1 overexpression/knockdown, GSK3β selective inhibitors, proteasome inhibitor, co-immunoprecipitation, site-directed analysis of NDRG1 C-terminal domain phosphorylation, in vitro/in vivo tumor models Cancer research Medium 31723002
2021 NDRG1 directly regulates androgen receptor (AR) signaling in prostate cancer: NDRG1 promotes AR interaction with HSP90 (shown by Co-IP), which stabilizes AR while decreasing its androgen-mediated activation; NDRG1 suppresses AR phosphorylation (p-ARSer213, p-ARSer81), PSA expression, and AR transcriptional activity partly by reducing c-Jun phosphorylation and inhibiting the c-Jun-AR interaction. The CAP domain of NDRG1 is identified as vital for inhibition of AR activity. Co-immunoprecipitation (AR-HSP90, AR-c-Jun), NDRG1 overexpression/siRNA, domain deletion mutants, phosphorylation Western blots, PSA reporter assay, patient prostatectomy specimens The Journal of biological chemistry High 34785213
2021 N-cadherin suppresses NDRG1 expression through a c-Jun/AR/DNMT1 complex that binds TRE elements in the NDRG1 promoter and induces DNA hypermethylation, establishing a mechanistic axis (N-cadherin→c-Jun→epigenetic suppression of NDRG1) that promotes EMT and castration-resistant prostate cancer progression. ChIP assay (c-Jun, AR, DNMT1 on NDRG1 promoter TRE region), bisulfite sequencing, co-immunoprecipitation, N-cadherin knockdown/overexpression, NDRG1 promoter methylation analysis International journal of biological sciences Medium 34512147
2022 NDRG1 acts as a critical mediator of endothelial inflammation: NDRG1 interacts with nuclear receptor Nur77 and functionally inhibits Nur77 transcriptional activity as well as NF-κB transcriptional activity; NDRG1 knockdown substantially attenuates IL-1β- and TNF-α-induced cytokine/chemokine and adhesion molecule expression, and inhibits MAPK/c-Jun/AP-1 activation. Endothelial cell-specific NDRG1 knockout mice show attenuated neointima formation, atherosclerosis, and arterial thrombosis. Co-immunoprecipitation (NDRG1-Nur77), shRNA lentiviral knockdown, luciferase reporter assays (Nur77, NF-κB, AP-1), endothelial-specific conditional knockout mice, carotid artery ligation model, thrombosis model Circulation research High 36562299
2023 Fasting-induced mTORC2 activation phosphorylates NDRG1 at Ser336, and phospho-NDRG1 engages with mitochondria to facilitate DRP1-independent mitochondrial fission and sustain respiratory sufficiency; a phosphorylation-deficient NDRG1Ser336Ala mutant fails to engage mitochondria or facilitate fission. mTORC2-phosphorylated NDRG1 cooperates with CDC42 and its effectors/regulators to orchestrate fission. Time-lapse live imaging, proteomics, siRNA screen, epistasis (Rictor KO, NDRG1Ser336Ala mutant, Cdc42-deficient cells), phospho-specific antibodies, DRP1-KO cells Nature cell biology High 37386153
2022 In zebrafish, Ndrg1a binds to the sodium-potassium ATPase (NKA) pump under anoxia and is required for its degradation, thereby conserving ATP in the kidney and ionocytes during oxygen deprivation; sodium azide treatment (which increases lactate under normoxia) is sufficient to trigger NKA degradation in an Ndrg1a-dependent manner, placing Ndrg1a downstream of lactate signaling as a metabolic switch. Co-immunoprecipitation (Ndrg1a-NKA), ndrg1a mutant zebrafish, anoxia survival assays, kidney function assays, sodium azide treatment eLife Medium 36214665
2024 NDRG1 activates MHC-I expression in pancreatic ductal adenocarcinoma cells by preventing ATG9A-dependent lysosomal-autophagy degradation of MHC-I; NDRG1 knockdown reduces MHC-I surface levels, while NDRG1 overexpression or pharmacological activation increases MHC-I, promotes CD8+ T cell infiltration and anti-tumor immunity, and overcomes resistance to immune checkpoint blockade in mouse PDAC models. Co-immunoprecipitation (NDRG1-ATG9A interaction), RNA sequencing, autophagy/proteasome inhibitors, orthotopic PDAC tumor models, flow cytometry (CD8+ T cells), multiplex immunofluorescence Drug resistance updates Medium 38228036
2024 NSUN6-mediated m5C modification of NDRG1 mRNA promotes NDRG1 mRNA stability via the m5C reader ALYREF, which binds specifically to m5C-labeled NDRG1 mRNA; elevated NDRG1 expression promotes homologous recombination-mediated DNA repair, conferring radioresistance in cervical cancer. m5C-seq, mRNA-seq, RNA immunoprecipitation (ALYREF-NDRG1 mRNA), NSUN6 knockdown/overexpression, CDX and 3D PDO models, LC-MS/MS quantification of m5C Molecular cancer Medium 38970106

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2004 Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 1159 15302935
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Large-scale mapping of human protein-protein interactions by mass spectrometry. Molecular systems biology 733 17353931
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
1998 Different requirements for EDS1 and NDR1 by disease resistance genes define at least two R gene-mediated signaling pathways in Arabidopsis. Proceedings of the National Academy of Sciences of the United States of America 575 9707643
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene 492 8125298
2004 RTP family members induce functional expression of mammalian odorant receptors. Cell 474 15550249
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2005 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. Genome research 409 16344560
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2009 Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR). The Biochemical journal 395 19402821
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
1996 Homocysteine-respondent genes in vascular endothelial cells identified by differential display analysis. GRP78/BiP and novel genes. The Journal of biological chemistry 317 8939898
2000 N-myc downstream-regulated gene 1 is mutated in hereditary motor and sensory neuropathy-Lom. American journal of human genetics 298 10831399
2004 Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3. The Biochemical journal 296 15461589
2000 Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer. Cancer research 285 10676663
2017 Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proceedings of the National Academy of Sciences of the United States of America 282 28611215
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2004 Iron chelators with high antiproliferative activity up-regulate the expression of a growth inhibitory and metastasis suppressor gene: a link between iron metabolism and proliferation. Blood 271 15251988
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2002 Expression of NDRG1, a differentiation-related gene, in human tissues. Histochemistry and cell biology 173 12432451
2013 mTOR target NDRG1 confers MGMT-dependent resistance to alkylating chemotherapy. Proceedings of the National Academy of Sciences of the United States of America 152 24367102
2021 Structure of the SARS-CoV-2 RNA-dependent RNA polymerase in the presence of favipiravir-RTP. Proceedings of the National Academy of Sciences of the United States of America 142 33526596
2006 Tumor growth suppression in pancreatic cancer by a putative metastasis suppressor gene Cap43/NDRG1/Drg-1 through modulation of angiogenesis. Cancer research 138 16778198
2012 SR1, a calmodulin-binding transcription factor, modulates plant defense and ethylene-induced senescence by directly regulating NDR1 and EIN3. Plant physiology 134 22345509
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2004 Overexpression of the plasma membrane-localized NDR1 protein results in enhanced bacterial disease resistance in Arabidopsis thaliana. The Plant journal : for cell and molecular biology 114 15447649
2009 MST2- and Furry-mediated activation of NDR1 kinase is critical for precise alignment of mitotic chromosomes. Current biology : CB 94 19327996
2007 Cytoplasmic recycling of 60S preribosomal factors depends on the AAA protein Drg1. Molecular and cellular biology 88 17646390
1999 The differentiation-related gene 1, Drg1, is markedly upregulated by androgens in LNCaP prostatic adenocarcinoma cells. FEBS letters 86 10428464
2004 Human Mob proteins regulate the NDR1 and NDR2 serine-threonine kinases. The Journal of biological chemistry 84 15067004
2013 The role of NDRG1 in the pathology and potential treatment of human cancers. Journal of clinical pathology 82 23750037
2006 Early responses in the Arabidopsis-Verticillium longisporum pathosystem are dependent on NDR1, JA- and ET-associated signals via cytosolic NPR1 and RFO1. Molecular plant-microbe interactions : MPMI 77 16941900
2000 Phosphorylation of RTP, an ER stress-responsive cytoplasmic protein. Biochemical and biophysical research communications 76 10860807
2019 Pharmacological targeting and the diverse functions of the metastasis suppressor, NDRG1, in cancer. Free radical biology & medicine 72 31132412
2013 NDRG1 functions in LDL receptor trafficking by regulating endosomal recycling and degradation. Journal of cell science 71 23813961
2003 Downregulation of Cap43 gene by von Hippel-Lindau tumor suppressor protein in human renal cancer cells. International journal of cancer 63 12767066
2023 Fused-Ring Pyrrole-Based Near-Infrared Emissive Organic RTP Material for Persistent Afterglow Bioimaging. Angewandte Chemie (International ed. in English) 62 38081786
2010 Ablation of the kinase NDR1 predisposes mice to the development of T cell lymphoma. Science signaling 60 20551432
2012 Rlp24 activates the AAA-ATPase Drg1 to initiate cytoplasmic pre-60S maturation. The Journal of cell biology 59 23185031
2005 Drg1 expression in 131 colorectal liver metastases: correlation with clinical variables and patient outcomes. Clinical cancer research : an official journal of the American Association for Cancer Research 57 15867226
2022 NDRG1 Signaling Is Essential for Endothelial Inflammation and Vascular Remodeling. Circulation research 56 36562299
2002 NHL25 and NHL3, two NDR1/HIN1-1ike genes in Arabidopsis thaliana with potential role(s) in plant defense. Molecular plant-microbe interactions : MPMI 56 12059109
2011 Ndrg1 in development and maintenance of the myelin sheath. Neurobiology of disease 54 21303696
2009 N-myc downstream regulated gene-1/Cap43 may play an important role in malignant progression of prostate cancer, in its close association with E-cadherin. Human pathology 53 19800102
2004 Function of Drg1/Rit42 in p53-dependent mitotic spindle checkpoint. The Journal of biological chemistry 53 15247272
2013 HIF-1α up-regulates NDRG1 expression through binding to NDRG1 promoter, leading to proliferation of lung cancer A549 cells. Molecular biology reports 52 23526365
2013 The drug diazaborine blocks ribosome biogenesis by inhibiting the AAA-ATPase Drg1. The Journal of biological chemistry 52 24371142
2002 The RTP site shared by the HIV-1 Tat protein and the 11S regulator subunit alpha is crucial for their effects on proteasome function including antigen processing. Journal of molecular biology 52 12419264
2011 The role of NDR1 in pathogen perception and plant defense signaling. Plant signaling & behavior 50 21758001
2005 Identification of DRG family regulatory proteins (DFRPs): specific regulation of DRG1 and DRG2. Genes to cells : devoted to molecular & cellular mechanisms 49 15676025
2022 NDRG1 in Cancer: A Suppressor, Promoter, or Both? Cancers 48 36497221
2012 NDRG1/Cap43/Drg-1 may predict tumor angiogenesis and poor outcome in patients with lung cancer. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 48 22481237
2024 NSUN6-mediated 5-methylcytosine modification of NDRG1 mRNA promotes radioresistance in cervical cancer. Molecular cancer 47 38970106
2020 m6A-dependent up-regulation of DRG1 by METTL3 and ELAVL1 promotes growth, migration, and colony formation in osteosarcoma. Bioscience reports 46 32266933
2017 Interplay of the iron-regulated metastasis suppressor NDRG1 with epidermal growth factor receptor (EGFR) and oncogenic signaling. The Journal of biological chemistry 44 28615452
2011 Phosphorylation of NDRG1 is temporally and spatially controlled during the cell cycle. Biochemical and biophysical research communications 44 21708134
2021 The Oncogenic Signaling Disruptor, NDRG1: Molecular and Cellular Mechanisms of Activity. Cells 43 34572031
2016 NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway. Cancer biology & therapy 43 27414086
2001 Ni(II) and Cu(II) binding with a 14-aminoacid sequence of Cap43 protein, TRSRSHTSEGTRSR. Journal of inorganic biochemistry 39 11330481
2023 mTORC2-NDRG1-CDC42 axis couples fasting to mitochondrial fission. Nature cell biology 38 37386153
2022 NDRG1 in Aggressive Breast Cancer Progression and Brain Metastasis. Journal of the National Cancer Institute 38 34893874
2017 NDR1-Dependent Regulation of Kindlin-3 Controls High-Affinity LFA-1 Binding and Immune Synapse Organization. Molecular and cellular biology 38 28137909
2016 Overexpression of the NDR1/HIN1-Like Gene NHL6 Modifies Seed Germination in Response to Abscisic Acid and Abiotic Stresses in Arabidopsis. PloS one 38 26849212
2007 Immunohistochemical expressions of Cap43 and Mina53 proteins in neuroblastoma. Journal of pediatric surgery 37 18022432
2005 HIV-1 incorporates and proteolytically processes human NDR1 and NDR2 serine-threonine kinases. Virology 36 15582665
2003 Identification and characterization of Xenopus NDRG1. Biochemical and biophysical research communications 36 12943662
2019 Long noncoding RNA CCAT2 promotes hepatocellular carcinoma proliferation and metastasis through up-regulation of NDRG1. Experimental cell research 35 30922920
2015 Ndrg1 is a T-cell clonal anergy factor negatively regulated by CD28 costimulation and interleukin-2. Nature communications 34 26507712
2003 Cellular distribution of NDRG1 protein in the rat kidney and brain during normal postnatal development. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 34 14566023
2017 The ubiquitin ligase Cullin5SOCS2 regulates NDR1/STK38 stability and NF-κB transactivation. Scientific reports 33 28216640
2014 MicroRNA-769-3p down-regulates NDRG1 and enhances apoptosis in MCF-7 cells during reoxygenation. Scientific reports 33 25081069
2020 Hypoxia-induced elevated NDRG1 mediates apoptosis through reprograming mitochondrial fission in HCC. Gene 32 32165297
2019 Bidirectional Regulation between NDRG1 and GSK3β Controls Tumor Growth and Is Targeted by Differentiation Inducing Factor-1 in Glioblastoma. Cancer research 31 31723002
2013 Soybean NDR1-like proteins bind pathogen effectors and regulate resistance signaling. The New phytologist 31 24372490
2015 NDRG1 links p53 with proliferation-mediated centrosome homeostasis and genome stability. Proceedings of the National Academy of Sciences of the United States of America 30 26324937
2014 Constitutively active NDR1-PIF kinase functions independent of MST1 and hMOB1 signalling. Cellular signalling 30 24747552
2001 Structure of the RTP-DNA complex and the mechanism of polar replication fork arrest. Nature structural biology 30 11224562
2022 HJURP regulates cell proliferation and chemo-resistance via YAP1/NDRG1 transcriptional axis in triple-negative breast cancer. Cell death & disease 29 35459269
2021 The metastasis suppressor NDRG1 directly regulates androgen receptor signaling in prostate cancer. The Journal of biological chemistry 29 34785213
2015 Fucoidan protects hepatocytes from apoptosis and inhibits invasion of hepatocellular carcinoma by up-regulating p42/44 MAPK-dependent NDRG-1/CAP43. Acta pharmaceutica Sinica. B 28 26713269
2008 Copper(II) binding to Cap43 protein fragments. Dalton transactions (Cambridge, England : 2003) 28 18985244
2018 Downregulated NDR1 protein kinase inhibits innate immune response by initiating an miR146a-STAT1 feedback loop. Nature communications 27 30018336
2017 Ndrg1 promotes adipocyte differentiation and sustains their function. Scientific reports 27 28775290
2009 An NMR study on nickel binding sites in Cap43 protein fragments. Dalton transactions (Cambridge, England : 2003) 27 19587996
2021 The Phytophthora effector Avh241 interacts with host NDR1-like proteins to manipulate plant immunity. Journal of integrative plant biology 26 33586843
2013 Aberrant NDRG1 methylation associated with its decreased expression and clinicopathological significance in breast cancer. Journal of biomedical science 26 23899187
2012 RAMP like proteins : RTP and REEP family of proteins. Advances in experimental medicine and biology 26 22434109
2020 GR, Sgk1, and NDRG1 in esophageal squamous cell carcinoma: their correlation with therapeutic outcome of neoadjuvant chemotherapy. BMC cancer 25 32106831
2020 The Emerging Roles of NDR1/2 in Infection and Inflammation. Frontiers in immunology 25 32265942
2008 Correlation between NDRG1 and PTEN expression in endometrial carcinoma. Cancer science 25 18377423
2019 The metastasis suppressor, NDRG1, differentially modulates the endoplasmic reticulum stress response. Biochimica et biophysica acta. Molecular basis of disease 24 30981813
2015 Regulation of NDR1 activity by PLK1 ensures proper spindle orientation in mitosis. Scientific reports 24 26057687
2011 N-myc downstream regulated gene1/Cap43 overexpression suppresses tumor growth by hepatic cancer cells through cell cycle arrest at the G0/G1 phase. Cancer letters 24 21775055
2009 NDRG1 and CRK-I/II are regulators of endothelial cell migration under Intermittent Hypoxia. Angiogenesis 24 19760510
2009 Independent stabilizations of polysomal Drg1/Dfrp1 complex and non-polysomal Drg2/Dfrp2 complex in mammalian cells. Biochemical and biophysical research communications 24 19819225
2017 Developmentally Regulated GTP binding protein 1 (DRG1) controls microtubule dynamics. Scientific reports 23 28855639
2023 CRISPR/Cas9 Screen in Gastric Cancer Patient-Derived Organoids Reveals KDM1A-NDRG1 Axis as a Targetable Vulnerability. Small methods 22 36908010
2020 LINC01419 promotes cell proliferation and metastasis in hepatocellular carcinoma by enhancing NDRG1 promoter activity. Cellular oncology (Dordrecht, Netherlands) 22 32557341
2018 HER4 promotes cell survival and chemoresistance in osteosarcoma via interaction with NDRG1. Biochimica et biophysica acta. Molecular basis of disease 22 29524631
2023 The role of the NDRG1 in the pathogenesis and treatment of breast cancer. Biochimica et biophysica acta. Reviews on cancer 21 36841367
2021 The role of N-cadherin/c-Jun/NDRG1 axis in the progression of prostate cancer. International journal of biological sciences 21 34512147
2018 Histone Deacetylase Inhibition Restores Expression of Hypoxia-Inducible Protein NDRG1 in Pancreatic Cancer. Pancreas 21 29303911
2015 SUMO modification regulates the protein stability of NDRG1. Biochemical and biophysical research communications 21 25712528
2015 NDR1 modulates the UV-induced DNA-damage checkpoint and nucleotide excision repair. Biochemical and biophysical research communications 21 25912875
2004 Nickel(II) binding to Cap43 protein fragments. Journal of inorganic biochemistry 21 15149799
1999 Site-directed mutants of RTP of Bacillus subtilis and the mechanism of replication fork arrest. Journal of molecular biology 21 10064700
2024 NDRG1 overcomes resistance to immunotherapy of pancreatic ductal adenocarcinoma through inhibiting ATG9A-dependent degradation of MHC-1. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 20 38228036
2018 NDRG1 Downregulates ATF3 and Inhibits Cisplatin-Induced Cytotoxicity in Lung Cancer A549 Cells. International journal of medical sciences 20 30443171
2017 Increased NDRG1 expression attenuate trophoblast invasion through ERK/MMP-9 pathway in preeclampsia. Placenta 20 28292472
2022 Overexpression of NDR1 leads to pathogen resistance at elevated temperatures. The New phytologist 19 35488494
2018 Different effects of long noncoding RNA NDRG1-OT1 fragments on NDRG1 transcription in breast cancer cells under hypoxia. RNA biology 19 30497328
2023 The Myc Family and the Metastasis Suppressor NDRG1: Targeting Key Molecular Interactions with Innovative Therapeutics. Pharmacological reviews 18 37280098
2022 NDR1 increases NOTCH1 signaling activity by impairing Fbw7 mediated NICD degradation to enhance breast cancer stem cell properties. Molecular medicine (Cambridge, Mass.) 18 35508987
2022 N-myc downstream regulated gene 1 (ndrg1) functions as a molecular switch for cellular adaptation to hypoxia. eLife 18 36214665
2012 NDR1/STK38 potentiates NF-κB activation by its kinase activity. Cell biochemistry and function 18 22674419