| 2001 |
NDFIP1 (N4WBP5) binds Nedd4 family WW domains via two PPXY motifs in its amino terminus, is itself ubiquitinated, localizes to the Golgi complex, and its ectopic expression disrupts Golgi structure, suggesting a role as an adaptor for Nedd4-like proteins in ubiquitin-dependent protein sorting. |
Co-immunoprecipitation/WW-domain binding assays, subcellular fractionation, immunofluorescence, overexpression morphological analysis |
The Journal of biological chemistry |
High |
11748237
|
| 2006 |
Ndfip1 promotes the function of the E3 ubiquitin ligase Itch to ubiquitinate and reduce the half-life of JunB in T cells; absence of Ndfip1 leads to JunB accumulation, Th2 cytokine production, and inflammatory disease. T cell activation promotes Ndfip1 expression and its physical association with Itch. |
Ndfip1 knockout mouse, co-immunoprecipitation, JunB half-life measurement, T cell functional assays |
Immunity |
High |
17137798
|
| 2008 |
Ndfip1 is sorted into exosomes and increases exosome secretion from cells; Ndfip1 expression recruits Nedd4, Nedd4-2, and Itch (which are otherwise absent) into exosomes, providing a mechanism for cargo-mediated removal of Nedd4 family proteins via the multivesicular body/exosome pathway. |
Exosome isolation and characterization, transfection overexpression, primary neuron exosome analysis, Western blot |
The Journal of biological chemistry |
Medium |
18819914
|
| 2009 |
Ndfip1 acts as an adaptor that binds DMT1 in response to iron or cobalt exposure in human neurons, recruits the E3 ligase Nedd4-2 to ubiquitinate DMT1, leading to DMT1 degradation, reduced metal entry, and protection from metal toxicity. Ndfip1 knockout mice accumulate iron in neurons. |
Co-immunoprecipitation, shRNAi knockdown, overexpression, ubiquitination assay, metal toxicity assay, Ndfip1−/− mouse brain analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
19706893
|
| 2010 |
Ndfip1 and Ndfip2 associate with the EGF receptor and PTEN and control ubiquitination and protein abundance of PTEN, c-Cbl, and Src family kinases; depletion of Ndfip1 inhibits Akt activation in EGF-stimulated HeLa cells, stimulates Jnk activation, and enhances cell multiplication. Ndfip2 (but not Ndfip1) is phosphorylated by Src/Lyn and can scaffold Src phosphorylation of Ndfip1. |
siRNA depletion, co-immunoprecipitation, ubiquitination assay, EGF signaling pathway analysis, cell proliferation assay |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
20534535
|
| 2010 |
Ndfip1 knockout mice fed a low-iron diet show significantly higher DMT1 expression and activity in duodenal enterocytes, elevated serum iron and transferrin saturation, and increased liver/spleen iron stores, demonstrating that Ndfip1 is a critical in vivo regulator of DMT1 and systemic iron homeostasis. |
Ndfip1−/− mouse model, intestinal iron absorption assay, serum iron measurement, tissue iron quantification, Ndfip1−/−/Rag1−/− immunodeficient mice |
Blood |
High |
20959604
|
| 2011 |
TGF-β signaling transiently induces Ndfip1 expression during iTreg differentiation; once expressed, Ndfip1 promotes Itch-mediated ubiquitination and degradation of JunB, preventing IL-4 production and permitting sustained Foxp3 expression and iTreg cell differentiation. |
Ndfip1−/− T cell in vitro differentiation assays, cytokine measurement, JunB protein level analysis, TGF-β stimulation experiments |
Nature immunology |
High |
22080920
|
| 2012 |
Ndfip1 is required for the translocation of cytoplasmic Pten into neuronal nuclei after cerebral ischemia; Ndfip1 binds Pten, enhances its ubiquitination by Nedd4 E3 ligases, and increases the rate of Pten nuclear import as measured by FRAP. Ndfip1-deficient neurons fail to import Pten and suffer larger infarcts with suppressed pAkt activation. |
Ndfip1−/− mouse ischemia model, co-immunoprecipitation, ubiquitination assay, FRAP live imaging, infarct size measurement, pAkt Western blot |
The Journal of cell biology |
High |
22213801
|
| 2012 |
Ndfip1 negatively regulates RIG-I-dependent antiviral signaling by enhancing Smurf1 self-ubiquitination and facilitating Smurf1 interaction with MAVS, promoting K48-linked ubiquitination and proteasomal degradation of MAVS. Ndfip1 knockdown elevates MAVS levels and amplifies IFN-β and NF-κB signaling. |
Overexpression, siRNA knockdown, co-immunoprecipitation, luciferase reporter assays, IRF-3 phosphorylation assay, ubiquitination assay |
Journal of immunology |
Medium |
23087404
|
| 2012 |
Endogenous Ndfip1 binds Nedd4-2 in the brain (with or without ischemia), as confirmed by immunoprecipitation. Ischemia-induced Itch upregulation promotes neuronal survival independently of Ndfip1. |
Co-immunoprecipitation from brain tissue, immunohistochemistry, ischemia model in rats |
Experimental neurology |
Medium |
22417925
|
| 2014 |
Rab5 GTPase cooperates with Ndfip1 in Pten ubiquitination and nuclear trafficking; Rab5 colocalizes with Pten on endosomes, dominant-negative Rab5 reduces Pten ubiquitination and nuclear import, and Ndfip1 deletion abrogates nuclear trafficking of ubiquitinated Pten even in the presence of Rab5. |
Bimolecular fluorescence complementation (BiFC) for protein interaction imaging, dominant-negative Rab5 expression, Ndfip1 genomic deletion, co-immunoprecipitation, ubiquitination assay |
Traffic |
Medium |
24798731
|
| 2015 |
Ndfip1 mediates ubiquitination of BRAT1 (a BRCA1-associated ATM activator), which is required for BRAT1 nuclear translocation during the DNA damage response. Without Ndfip1, BRAT1 fails to enter the nucleus and ATM phosphorylation is not maintained. Genotoxic stress increases both Ndfip1 and phospho-ATM levels. |
Co-immunoprecipitation, overexpression/knockdown, nuclear fractionation, genotoxic stress assays, brain injury model immunostaining |
The Journal of biological chemistry |
Medium |
25631046
|
| 2015 |
Ndfip1 controls Pten nuclear compartmentalization during the cell cycle; Ndfip1 deletion abolishes nuclear Pten without affecting cytoplasmic Pten-PI3K/Akt activity, leading to dysregulated Plk1 and cyclin D1 levels and increased cell proliferation. Transgenic Ndfip1 overexpression in the developing brain increases nuclear Pten, lengthens neuronal progenitor cell cycle, and causes microencephaly. |
Ndfip1 genetic deletion, subcellular fractionation, cell proliferation assays, brain transgenic overexpression, cyclin D1/Plk1 Western blot |
Journal of molecular cell biology |
Medium |
25801959
|
| 2015 |
Ndfip1 enhances Itch E3 ligase activity by recruiting the E2 ubiquitin-conjugating enzyme UbcH7 to Itch; the N-terminal region of Ndfip1 binds UbcH7 while its PY motif binds Itch, making Ndfip1 a scaffold/adaptor bridging E2 and E3. Ndfip1 facilitates Itch-mediated TAK1 ubiquitination and restrains proinflammatory cytokine production in airway inflammation. |
Co-immunoprecipitation, Ndfip1 mutant rescue experiments, ubiquitination assay, Ndfip1−/− and Itch−/− mouse airway inflammation model |
Journal of immunology |
High |
25632008
|
| 2016 |
Nedd4-2 and Ndfip1 limit IgE/FcεRI-mediated mast cell activation by ubiquitinating phosphorylated Syk tyrosine kinase, thereby attenuating downstream FcεRI signalosome activity. Loss of Nedd4-2 or Ndfip1 in mast cells results in exacerbated and prolonged IgE-mediated cutaneous anaphylaxis in vivo. |
Nedd4-2 and Ndfip1 knockout mast cells, ubiquitination assay for Syk, in vivo cutaneous anaphylaxis model |
Nature communications |
High |
27786273
|
| 2017 |
Ndfip1 restricts mTORC1 signaling and glycolysis in Treg cells; Ndfip1-deficient Tregs show elevated mTORC1 activity and glycolysis. Ndfip1 restricts IL-4 production and mTORC1 signaling via distinct mechanisms (IL-4 deficiency does not prevent mTORC1 elevation). Ndfip1 deletion in Tregs causes autoinflammatory disease with loss of Foxp3 expression. |
Treg-specific Ndfip1 conditional knockout, metabolic profiling (Seahorse), proteomics, mTORC1 signaling assays, Foxp3 lineage tracing |
Nature communications |
High |
28580955
|
| 2017 |
Ndfip1 promotes degradation of RORγT in Th17 cells; Ndfip1-deficient Th17 cells accumulate RORγT and have increased frequency, enhanced IL-17 production, and greater colitis-inducing capacity in vivo. |
Ndfip1−/− mouse, Th17 cell differentiation assays, RORγT protein level analysis, in vivo transfer colitis model |
Scientific reports |
Medium |
28051111
|
| 2022 |
NDFIP1 is required for hepcidin-induced ubiquitination and degradation of ferroportin (the iron export channel); siRNA depletion of NDFIP1 prevents BMP6- and exogenous hepcidin-induced ferroportin degradation in HepG2 cells, and AAV-mediated silencing of Ndfip1 in mouse liver increases hepatic ferroportin and circulating iron. |
siRNA screen of 88 ubiquitin pathway components, FPN-GFP inducible reporter cell line, AAV-mediated in vivo silencing, serum iron measurement |
Haematologica |
High |
34320783
|
| 2023 |
NDFIP1 limits cellular TAZ (WWTR1) accumulation by packaging it into exosomes; NDFIP1 interacts with TAZ via WW-domain recognition, and NDFIP1 knockout leads to TAZ accumulation without changes in mRNA or degradation rate. NDFIP1-mediated TAZ exosomal export suppresses NSCLC cell proliferation in vitro and in vivo. |
Co-immunoprecipitation, exosome isolation, NDFIP1 knockout, cell proliferation assays, xenograft mouse model |
Protein & cell |
Medium |
36929005
|
| 2024 |
NDFIP1 directly interacts with the TRESK (KCNK18) background potassium channel and negatively regulates its current; coexpression of NDFIP1 abolishes TRESK current in Xenopus oocytes, dependent on intact PPxY motifs (required for Nedd4 interaction) and partially reversed by dominant-negative Nedd4. NDFIP1 coexpression induces ubiquitination of TRESK. |
Xenopus oocyte two-electrode voltage clamp, co-immunoprecipitation, PPxY motif mutagenesis, dominant-negative Nedd4 overexpression, ubiquitination assay |
International journal of molecular sciences |
Medium |
39201565
|
| 2013 |
Ndfip1 is required for the normal development of pyramidal neuron dendrites and dendritic spines in the neocortex; conditional knockout neurons show stunted dendritic arbors, fewer spines, reduced postsynaptic density proteins (Arc, PSD-95), and altered PI3K/Akt signaling. |
Conditional neuron-specific Ndfip1 knockout mouse, electron microscopy, dendritic morphology analysis, PSD fractionation, Western blot for signaling components |
Cerebral cortex |
Medium |
23897647
|
| 2023 |
Ndfip1 acts as a negative regulator of spatial memory formation; spatial training decreases Ndfip1 expression and reduces its association with Nedd4-1, leading to decreased ubiquitination of Beclin 1 and PTEN in the hippocampus and increased levels of both proteins. Ndfip1 conditional heterozygous mice show enhanced spatial memory. |
Co-immunoprecipitation, ubiquitination assay in hippocampal tissue, conditional heterozygous and KO mice, water maze behavioral testing |
PloS one |
Medium |
37023120
|