Affinage

NEDD4

E3 ubiquitin-protein ligase NEDD4 · UniProt P46934

Length
1319 aa
Mass
149.1 kDa
Annotated
2026-06-10
100 papers in source corpus 48 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NEDD4 (NEDD4-1) is a HECT-domain E3 ubiquitin ligase that controls the abundance and trafficking of membrane receptors, ion channels, and signaling proteins, governing diverse processes from epithelial Na+ transport and synaptic transmission to growth-factor signaling, tumor suppression, and cell death (PMID:10720933, PMID:10882424, PMID:21338354, PMID:25692647). Substrate selection is driven principally by recognition of PY (PPxY) motifs through its WW domains, as established for ENaC subunits, ErbB4 CYT-1, and VDAC1 (PMID:10720933, PMID:10882424, PMID:19193720, PMID:37139424), while its C2 domain mediates Ca2+-dependent membrane localization and constitutive adaptor binding (Grb10) (PMID:10720933, PMID:10882424, PMID:10446181). The ligase assembles ubiquitin chains of multiple linkages to dictate substrate fate: K48-linked chains target PD-L1, VDAC1, TAK1, and Mdm2 for proteasomal degradation (PMID:34753771, PMID:37139424, PMID:38569496), whereas K63- and K27-linked chains can be non-degradative, stabilizing Mdm2 and VHL or potentiating TGFBR1 signaling (PMID:24413081, PMID:32792353, PMID:35501461). Beyond catalyzing degradation, NEDD4 acts as a non-degradative scaffold: K29-linked auto-ubiquitination at K1279 recruits the deubiquitinase USP13 to protect VPS34 from K48 chains and promote autophagy (PMID:32101753). NEDD4 ubiquitinates numerous receptors for endocytic downregulation, frequently using arrestin or NDFIP adaptors to bridge substrate recognition—β-arrestin recruits NEDD4 to the agonist-activated β2-adrenergic and mGlu7 receptors, and to NHE1, while NDFIP1/2 bridge it to aquaporin-2 (PMID:18544533, PMID:31373553, PMID:20855896, PMID:28931009). Its activity is tightly autoregulated: WW-domain linker regions and an oligomerization-promoting HECT α1 lysine impose intramolecular autoinhibition that is relieved by NDFIP1, PPxY adaptors (LRAD3), or substrate-directed phosphorylation by GRK2 and FGFR3 (PMID:28069708, PMID:31578285, PMID:17544362, PMID:26854353, PMID:34753771). NEDD4 also ubiquitinates nuclear substrates including histone H3, where glucose-dependent H3 ubiquitination recruits GCN5 to activate transcription (PMID:28300060). NEDD4 is reported as an E3 ligase for PTEN, but two independent Nedd4-1 knockout mouse lines found no effect on PTEN interaction, stability, or downstream Akt activity, leaving the physiological relevance of this substrate unresolved (PMID:17218260, PMID:18562292).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    Established the core substrate-recognition logic of NEDD4 by showing WW-domain engagement of PY motifs drives ubiquitination and surface downregulation of a physiological ion channel.

    Evidence Co-IP, electrophysiology, PY-motif mutagenesis (Liddle's mutations), and C2-domain localization in polarized MDCK cells for ENaC

    PMID:10720933 PMID:10882424

    Open questions at the time
    • Did not resolve ubiquitin chain linkage type on ENaC
    • Regulation of NEDD4 activity itself not addressed
  2. 2001 High

    Showed that kinase phosphorylation can regulate NEDD4-family channel control, defining a signaling input to the ENaC pathway.

    Evidence Co-IP, in vitro kinase assay, and Na+ current measurement of SGK acting on NEDD4/NEDD4-2

    PMID:11696533

    Open questions at the time
    • SGK phosphorylates NEDD4-2 but not NEDD4, leaving NEDD4 regulation here open
    • Structural basis of phospho-dependent affinity change not defined
  3. 2007 High

    Proposed PTEN as a NEDD4 substrate linking the ligase to PI3K/Akt and transformation, the first oncogenic role assigned.

    Evidence Biochemical E3 purification, in vitro and cell ubiquitination, and xenograft model

    PMID:17218260

    Open questions at the time
    • Physiological relevance contested by subsequent KO data
    • In vivo requirement not tested with genetic loss-of-function in this study
  4. 2008 High

    Directly challenged the PTEN-substrate model using genetic loss-of-function, establishing that NEDD4 substrate assignments require in vivo validation.

    Evidence Two independent Nedd4-1 KO mouse strains, co-IP attempts, and PTEN stability/Akt readouts in MEFs

    PMID:18562292

    Open questions at the time
    • Does not exclude context- or tissue-specific PTEN regulation
    • Cannot rule out redundancy with NEDD4L
  5. 2008 High

    Defined arrestin-bridged recruitment as a mechanism for NEDD4 targeting of GPCRs, generalizing beyond direct PY recognition.

    Evidence β-arrestin2 knockdown, dominant-negative NEDD4, complex co-IP, and lysosomal trafficking assay for β2AR

    PMID:18544533

    Open questions at the time
    • Ubiquitin chain linkage on β2AR not determined
    • Structural basis of arrestin-NEDD4 bridging not resolved
  6. 2011 High

    Showed NEDD4 attenuates receptor tyrosine kinase signaling via endocytic downregulation, and that recognition can occur through non-canonical non-PY motifs.

    Evidence Direct binding, in vitro/in vivo ubiquitination, endocytosis assay, FGFR1-Δ6 mutant, and zebrafish neuronal patterning for FGFR1

    PMID:21765395

    Open questions at the time
    • Generality of non-PY recognition across substrates unclear
    • Chain linkage directing FGFR1 endocytosis not specified
  7. 2011 High

    Extended NEDD4 control to neuronal AMPA receptors, linking the ligase to synaptic strength.

    Evidence Synaptosome co-IP, GluA1 K868R mutagenesis, siRNA knockdown, and mEPSC recording

    PMID:21338354

    Open questions at the time
    • Upstream signal triggering NEDD4-AMPAR engagement not defined
    • In vivo behavioral consequence not tested
  8. 2014 High

    Revealed linkage-specific non-degradative ubiquitination by showing NEDD4 stabilizes Mdm2 via K63 chains, distinct from degradative K48 control.

    Evidence Reconstituted in vitro ligase assay, Nedd4-1 KO MEFs, linkage analysis, CHX chase, and p53/cell-cycle readouts

    PMID:24413081

    Open questions at the time
    • How K63 stabilization opposes Mdm2 autoubiquitination mechanistically unclear
    • Physiological p53 contexts not fully mapped
  9. 2015 High

    Placed NEDD4 as a negative regulator of the Hippo tumor-suppressor pathway and a positive regulator of growth signaling, defining opposing pro-proliferative roles.

    Evidence In vitro ubiquitination, co-IP, protein stability, Drosophila ISC models for WW45/LATS, and IRS-2 monoubiquitination/Epsin1 recruitment with zebrafish growth assays

    PMID:25692647 PMID:25879670

    Open questions at the time
    • Switch between degradative and signaling-promoting outputs not unified mechanistically
    • Cross-talk with autoinhibition state not addressed
  10. 2017 High

    Uncovered NEDD4 as a non-degradative scaffold in autophagy, where self-K29-ubiquitination recruits a deubiquitinase to protect a third protein.

    Evidence Linkage-specific ubiquitination, NEDD4-1/USP13 KO cells, K1279/K419 mutagenesis, and autophagosome assays for the VPS34 complex

    PMID:32101753

    Open questions at the time
    • Trigger inducing K29 auto-ubiquitination unknown
    • Structural basis of USP13 recruitment by K29 chains not defined
  11. 2017 High

    Identified a nuclear/chromatin function for NEDD4, coupling glucose-dependent histone H3 ubiquitination to GCN5 recruitment and transcriptional activation.

    Evidence In vitro H3 ubiquitination, ChIP-seq, H3 lysine mutagenesis, GCN5 pulldown, and tumorsphere assays

    PMID:28300060

    Open questions at the time
    • How a cytoplasmic membrane ligase accesses chromatin not resolved
    • Metabolic signal linking glucose to NEDD4 activity unclear
  12. 2019 High

    Defined the molecular basis of NEDD4 autoinhibition and its allosteric relief, explaining how the ligase is held inactive and switched on.

    Evidence Oligomerization biophysics and HECT α1 lysine mutagenesis (28069708); WW-linker deletion/phosphomimic mutants and NDFIP1 activation across PTEN/p62/WBP2 (31578285)

    PMID:28069708 PMID:31578285

    Open questions at the time
    • In vivo prevalence of the oligomeric inactive state unknown
    • How phosphorylation by GRK2/FGFR3 intersects with linker autoinhibition not fully mapped
  13. 2020 High

    Established physiological roles of NEDD4 in development and cell-fate via genetic models, including spermatogonial homeostasis and myelination.

    Evidence Conditional Nedd4 KO mice with NANOS2 ubiquitination and stress-granule clearance (28585553); Daam2-VHL-NEDD4 K63 axis in oligodendrocyte differentiation with human MS lesion analysis (32792353)

    PMID:28585553 PMID:32792353

    Open questions at the time
    • Direct WW-PY recognition of these substrates not always demonstrated
    • Linkage-to-outcome rules across these substrates not unified
  14. 2021 High

    Linked NEDD4 to immune checkpoint and cell-death control, showing FGFR3-activated NEDD4 degrades PD-L1 and connecting it to ferroptosis regulation.

    Evidence K48-specific ubiquitination, NEDD4 KO cancer cells, in vivo tumor models for PD-L1 (34753771); VDAC2/3 ubiquitination in the FOXM1-NEDD4 ferroptosis loop (31974380)

    PMID:31974380 PMID:34753771

    Open questions at the time
    • FGFR3-dependent phospho-activation mechanism on NEDD4 not structurally defined
    • Selectivity among VDAC paralogs not fully explained
  15. 2024 Medium

    Demonstrated post-translational modification of NEDD4 itself (lactylation) as a substrate-selective regulatory switch, expanding the modes controlling its activity.

    Evidence Co-IP, ubiquitination assay, NEDD4 K33 lactylation detection/mutagenesis, and APAP liver injury model for Caspase-11

    PMID:38385085

    Open questions at the time
    • Single lab, single substrate context for lactylation
    • Whether lactylation affects other substrates not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NEDD4 integrates its autoinhibition state, adaptor repertoire, and diverse post-translational modifications to select among its many substrates and chain linkages in a given cellular context remains unresolved.
  • No unified model predicting substrate choice or chain-linkage output
  • Tissue-specific adaptor and modification landscapes uncharacterized
  • Physiological vs. overexpression-based substrate assignments not consistently distinguished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016740 transferase activity 5 GO:0016874 ligase activity 4 GO:0098772 molecular function regulator activity 2 GO:0042393 histone binding 1
Localization
GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 2 GO:0005634 nucleus 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 5 R-HSA-168256 Immune System 4 R-HSA-382551 Transport of small molecules 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-4839726 Chromatin organization 1 R-HSA-9612973 Autophagy 1
Partners
ARRB2GRB10GRK2LRAD3NDFIP1SGKUSP13YOD1
Complex memberships
NEDD4-USP13 complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 NEDD4-1 (NEDD4) was purified as the E3 ubiquitin ligase for PTEN; it catalyzes PTEN polyubiquitination in cells, leading to proteasomal degradation of PTEN and consequent activation of downstream PI3K/Akt signaling, potentiating cellular transformation. Biochemical purification of E3 ligase activity from cell lysates, in vitro ubiquitination assay, cell-based polyubiquitination assay, overexpression/knockdown with PTEN stability readout, xenograft tumor model Cell High 17218260
2008 Subsequent study using two independently generated Nedd4-1 knockout mouse strains found no detectable interaction between Nedd4-1 and PTEN, and PTEN stability, ubiquitination, subcellular distribution, and downstream Akt activity were all unchanged in Nedd4-1-deficient cells, failing to support Nedd4-1 as the physiological E3 ligase for PTEN. Nedd4-1 knockout MEFs (two independent mouse strains), co-immunoprecipitation attempts, PTEN stability assay, PKB/Akt activity assay, nuclear PTEN function (Rad51 transactivation assay) Proceedings of the National Academy of Sciences of the United States of America High 18562292
2000 NEDD4 binds the epithelial Na+ channel (ENaC) via its WW domains interacting with PY motifs (PPxY) in the C-termini of ENaC subunits, catalyzes ENaC ubiquitination via its HECT domain, and reduces ENaC surface expression; the C2 domain localizes NEDD4 to the apical plasma membrane in a Ca2+-dependent manner in polarized MDCK cells. Electrophysiology, co-immunoprecipitation, subcellular fractionation/localization, site-directed mutagenesis of PY motifs (Liddle's syndrome mutations), MDCK cell polarization experiments Kidney international High 10720933 10882424
2001 SGK (serum- and glucocorticoid-regulated kinase) binds to NEDD4 (and NEDD4-2) via a PY motif in SGK; SGK phosphorylates NEDD4-2 (but not NEDD4), reducing NEDD4-2 binding to αENaC and thereby relieving NEDD4-2-mediated inhibition of epithelial Na+ absorption. Co-immunoprecipitation, in vitro kinase assay (phosphorylation of recombinant NEDD4-2), electrophysiology (Na+ current measurement), deletion/mutation analysis of PY motif The Journal of biological chemistry High 11696533
2004 GRK2 (G-protein-coupled receptor kinase 2) phosphorylates the C-terminus of the ENaC β-subunit and renders ENaC insensitive to inhibition by NEDD4-2, maintaining channels in an active state. Electrophysiology, in vitro phosphorylation assay, co-expression in Xenopus oocytes Proceedings of the National Academy of Sciences of the United States of America Medium 15284439
2007 GRK2 directly interacts with and phosphorylates NEDD4 (as well as NEDD4-2) at multiple sites, including threonine 466 in NEDD4 located in the WW3 domain region that binds ENaC. Co-immunoprecipitation, in vitro kinase assay with recombinant proteins, mass spectrometry of phosphorylation sites Biochemical and biophysical research communications Medium 17544362
2008 NEDD4 acts as the E3 ubiquitin ligase for the β2-adrenergic receptor (β2AR); agonist stimulation triggers β-arrestin2-mediated recruitment of NEDD4 to activated β2AR, leading to NEDD4-catalyzed receptor ubiquitination and lysosomal degradation. β-arrestin2 is an essential adaptor, as its knockdown abolishes β2AR-NEDD4 interaction. Dominant-negative NEDD4 overexpression, siRNA knockdown (NEDD4, NEDD4-2, AIP4), co-immunoprecipitation of NEDD4–β-arrestin2–β2AR complex, ubiquitination assay, lysosomal trafficking assay The Journal of biological chemistry High 18544533
2011 NEDD4-1 directly binds and ubiquitylates activated FGFR1 via its WW3 domain interacting with a non-canonical non-PY motif on FGFR1, promoting FGFR1 endocytosis and attenuating downstream signaling (FRS2α, Akt, Erk1/2, PLCγ). FGFR1 lacking the Nedd4-1 recognition motif (FGFR1-Δ6) shows impaired endocytosis and sustained signaling; in neural stem cells promotes neuronal differentiation; in zebrafish disrupts anterior neuronal patterning. Direct binding assay, co-immunoprecipitation, in vitro/in vivo ubiquitination assay, receptor endocytosis assay, Nedd4-1 knockdown, FGFR1-Δ6 mutant in neural stem cells, zebrafish embryo expression The EMBO journal High 21765395
2011 NEDD4 is the E3 ubiquitin ligase responsible for AMPA receptor (AMPAR/GluA1) ubiquitination in neurons; NEDD4 co-localizes and associates with AMPARs in synaptoneurosomes, ubiquitinates GluA1 at K868, reduces AMPAR surface expression, and suppresses excitatory synaptic transmission. Knockdown of NEDD4 abolishes AMPAR ubiquitination. Co-immunoprecipitation, synaptosome fractionation, ubiquitination assay with lysine-to-arginine mutants (K868R), siRNA knockdown, electrophysiology (mEPSC recording) Journal of neurochemistry High 21338354
2014 NEDD4-1 is an E3 ubiquitin ligase for Mdm2; it interacts with Mdm2 via the Mdm2 RING domain and catalyzes K63-linked polyubiquitination of Mdm2 (distinct from K48-linked chains that Mdm2/MdmX forms), thereby stabilizing Mdm2. Nedd4-1 KO MEFs show increased p53 levels and activity, more robust DNA damage response, and increased G1 arrest. In vitro E3 ligase assay with recombinant proteins, Nedd4-1 KO MEF lysates, co-immunoprecipitation, ubiquitin linkage-specific analysis, Mdm2 half-life measurement (CHX chase), p53 reporter assays, cell cycle analysis Oncogene High 24413081
2014 NEDD4-1 acts as an E3 ubiquitin ligase for Ras; Ras signaling stimulates NEDD4-1 expression, but oncogenic Ras mutations or EGF signaling prevent NEDD4-1-mediated Ras ubiquitination, leading to NEDD4-1 accumulation and subsequent PTEN degradation. This defines a Ras–NEDD4-1–PTEN regulatory loop. In vivo ubiquitination assay, co-immunoprecipitation, expression analysis in human cancer samples and cancer cell lines, genetic rescue experiments Cell reports Medium 24746824
2015 NEDD4 ubiquitylates and destabilizes WW45 (SAV1) and LATS kinase (core Hippo pathway components), thereby suppressing Hippo signaling. MST1 protects WW45 but not LATS2 from NEDD4-mediated degradation. NEDD4 inactivation at high cell density enables contact inhibition via elevated Hippo activity. In Drosophila, NEDD4 promotes intestinal stem cell renewal by suppressing Hippo signaling. In vitro ubiquitination assay, co-immunoprecipitation, knockdown/overexpression with protein stability readouts, Drosophila genetic model (ISC proliferation) Nature communications High 25692647
2015 NEDD4 monoubiquitinates IRS-2, promoting its association with ubiquitin-binding protein Epsin1 and recruitment of IRS-2 to the membrane, thereby enhancing IGF-I receptor-induced IRS-2 tyrosine phosphorylation, downstream signaling, and cell proliferation. In zebrafish, NEDD4 overexpression accelerates embryonic growth through IRS-2. Co-immunoprecipitation, in vitro/in vivo ubiquitination assay, siRNA knockdown, membrane fractionation, IGF-I signaling assays, zebrafish embryo experiments Nature communications High 25879670
2015 Elevated NEDD4 is the E3 ubiquitin ligase responsible for HSF1 degradation induced by aggregated α-synuclein/proteotoxic stress; SIRT1-mediated deacetylation of HSF1 at K80 attenuates NEDD4-mediated HSF1 ubiquitination and stabilizes HSF1. Ubiquitination assay in neuroblastoma cells, siRNA knockdown of NEDD4, co-immunoprecipitation, pharmacological SIRT1 activation, site-directed mutagenesis (K80 acetylation), mouse model and human tissue validation Human molecular genetics Medium 26503960
2008 NEDD4 acts as the E3 ubiquitin ligase for the ErbB4 JM-a/CYT-1 intracellular domain (ICD); NEDD4 binds via its WW domains to three PY motifs in the CYT-1 C-terminus, catalyzes CYT-1 ICD ubiquitination, and promotes its proteasomal and lysosomal degradation. Mutation of PY motifs impairs NEDD4 binding, increases CYT-1 ICD stability, and (for one PY mutant) enhances nuclear translocation. Co-immunoprecipitation, in vitro direct binding assay, in vitro ubiquitination assay, PY motif mutagenesis, proteasome/lysosome inhibitor experiments FASEB journal High 19193720
2010 NEDD4-1 and β-arrestin-1 cooperate to ubiquitylate and internalize NHE1 (Na+/H+ exchanger 1) at the plasma membrane. β-arrestin-1 bridges NEDD4-1 to the NHE1 C-terminus; truncation of NHE1 C-terminus to aa550 abolishes β-arrestin-1 binding and NHE1 ubiquitylation. Knockout of either Nedd4-1 or β-arrestin-1 in mouse fibroblasts increases NHE1 surface levels and transport activity. Co-immunoprecipitation, siRNA knockdown, Nedd4-1 and β-arrestin-1 knockout mouse fibroblasts, ubiquitylation assay, surface biotinylation, ion transport assay The Journal of biological chemistry High 20855896
2008 NDFIP1 (Nedd4 family-interacting protein 1) recruits NEDD4 (and Nedd4-2 and Itch) into exosomes secreted from cells and primary neurons; without NDFIP1, these Nedd4 proteins are absent from exosomes. NDFIP1 increases overall exosome secretion. Exosome isolation, Western blot of exosomal fractions, co-transfection experiments, primary neuron exosome analysis The Journal of biological chemistry Medium 18819914
2017 NEDD4-1 undergoes K29-linked auto-ubiquitination at K1279, which serves as a scaffold to recruit the deubiquitinase USP13. The resulting NEDD4-1–USP13 complex removes K48-linked polyubiquitin chains from VPS34 at K419, stabilizing VPS34 and promoting autophagy flux. Knockout of either NEDD4-1 or USP13 increases K48-linked ubiquitination and degradation of VPS34. Co-immunoprecipitation, ubiquitination assay (linkage-specific), USP13/NEDD4-1 knockout cells, autophagosome formation assay, site-directed mutagenesis (K1279, K419) Cell reports High 32101753
2017 NEDD4 ubiquitinates histone H3 on lysine 23/36/37 residues in a glucose-dependent manner; this H3 ubiquitination specifically recruits histone acetyltransferase GCN5 for subsequent H3 K9 acetylation at transcription start sites and enhancer regions, activating transcription of IL1α, IL1β, and GCLM, and promoting tumour sphere formation. ChIP-seq, microarray, in vitro ubiquitination assay with recombinant H3, site-directed mutagenesis of H3 lysines, GCN5 pulldown, tumour sphere formation assay Nature communications High 28300060
2017 NEDD4 ubiquitylation activity is restrained by an evolutionarily conserved allosteric auto-inhibition mechanism: ubiquitylation of a conserved lysine on the HECT domain α1-helix promotes NEDD4 oligomerization (trimerization) that renders the ligase inactive. Arginine substitution of the ubiquitylated lysine impairs this inactivation and causes unrestrained FGFR1 ubiquitylation and constitutive IKS channel downregulation. Biochemical and biophysical analysis (oligomerization assays), site-directed mutagenesis, in vitro ubiquitination assays, electrophysiology (IKS channel), TIRF microscopy, genetic experiments in yeast The EMBO journal High 28069708
2019 NEDD4 catalytic activity is autoinhibited by WW domain linker regions that engage the HECT domain; allosteric activation by NDFIP1 (and engineered ubiquitin variants) relieves this autoinhibition. The WW domain linker also influences ubiquitin chain linkage (K48 vs K63) and degree of polyubiquitination on substrates. In vitro ubiquitination assays with recombinant NEDD4-1, linker deletion/phosphomimic mutants, NDFIP1 binding assays, substrate ubiquitination assays (PTEN, p62, WBP2) The Journal of biological chemistry High 31578285
1999 NEDD4 interacts constitutively with the adapter protein Grb10 (which couples to insulin and IGF-I receptors) via the C2 domain of NEDD4 and a region including the SH2/BPS domain of Grb10, both in yeast two-hybrid and by endogenous co-immunoprecipitation in mouse embryo fibroblasts; the interaction is Ca2+-independent. Yeast two-hybrid, co-immunoprecipitation of endogenous proteins in MEFs, deletion mutagenesis of Grb10 The Journal of biological chemistry Medium 10446181
2005 NEDD4 and NEDD4-2 share the same preferred ubiquitin-conjugating enzyme (E2) specificity: UbcH5b is the most efficient E2 for both ligases in vitro, with Ube2e3 used less efficiently. In vitro ubiquitination assay with panel of E2 enzymes and recombinant NEDD4/NEDD4-2 The international journal of biochemistry & cell biology Medium 16337426
2019 NEDD4 and NEDD4L (NEDD4-2) ubiquitinate LGR5 receptor (and DVL2), targeting them for proteasomal and lysosomal degradation; loss of Nedd4/Nedd4l enhances ISC proliferation and sensitivity to R-spondin and accelerates tumour development in Apcmin mice, demonstrating that NEDD4/NEDD4L negatively regulate Wnt/β-catenin signaling through LGR5 degradation. In vitro ubiquitination assay, co-immunoprecipitation, conditional KO mouse models, organoid culture, Apcmin tumour model, protein stability assays The EMBO journal High 31867777
2020 NEDD4 ubiquitinates VDAC2 and VDAC3 following erastin treatment, promoting their degradation; this suppresses erastin-induced ferroptosis. FOXM1-induced NEDD4 expression creates a negative feedback loop (FOXM1–NEDD4–VDAC2/3) that reduces ferroptosis sensitivity. siRNA knockdown of NEDD4, ubiquitination assay, co-immunoprecipitation, VDAC2/3 protein stability assay, ferroptosis assay (cell viability, lipid peroxidation) Nature communications High 31974380
2021 NEDD4, activated downstream of FGFR3, interacts with PD-L1 and catalyzes Lys48-linked polyubiquitination of PD-L1, targeting it for proteasomal degradation. Phosphorylation of NEDD4 by FGFR3 activates its E3 activity toward PD-L1. Co-immunoprecipitation, ubiquitination assay (K48-linkage specific), NEDD4 KO bladder cancer cell lines, FGFR3 inhibition experiments, tissue microarray, in vivo tumor mouse models Cancer research High 34753771
2020 NEDD4 controls spermatogonial progenitor cell (SPC) homeostasis by targeting the RNA-binding protein NANOS2 for ubiquitination/destabilization, promoting spermatogonial differentiation. NEDD4 is also required for stress granule (SG) clearance via the endosomal-lysosomal pathway during recovery from stress. Nedd4 conditional KO mice (spermatogonia), co-immunoprecipitation, ubiquitination assay, immunofluorescence (SG dynamics), lysosomal pathway inhibitor experiments Nature communications High 28585553
2013 NEDD4-1 promotes glioma cell migration and invasion by physically interacting with CNrasGEF and promoting its polyubiquitination and proteasomal degradation, thereby removing a migration suppressor. Co-immunoprecipitation, in vivo ubiquitination assay, siRNA knockdown/overexpression with migration and invasion assays (Transwell, wound healing), glioma tissue expression analysis PloS one Medium 24340059
2017 NEDD4 ubiquitinates and targets LATS1 (a core Hippo pathway kinase) for degradation in hepatocellular carcinoma cells, promoting tumor progression. siRNA knockdown/overexpression, co-immunoprecipitation, Western blot for LATS1 protein levels, cell proliferation/invasion assays Cell cycle Low 29480061
2017 NDFIP1 and NDFIP2 are essential adaptor proteins that bridge NEDD4 (and NEDD4L) to aquaporin-2 (AQP2), enabling NEDD4/NEDD4L-mediated AQP2 ubiquitination and lysosomal degradation; PY motifs in NDFIP1/2 are required for this function. siRNA knockdown in mpkCCD cells, Membrane Yeast Two-Hybrid (NDFIP2-AQP2 interaction), HEK293T co-transfection ubiquitination assay, NDFIP1/2 PY-motif mutants, AQP2 abundance assays PloS one Medium 28931009
2019 NEDD4 E3 ligase and β-arrestins regulate mGlu7 receptor ubiquitination and trafficking: upon agonist stimulation, β-arrestins recruit NEDD4 to mGlu7, facilitating NEDD4-mediated ubiquitination that promotes mGlu7 endocytosis and degradation by both proteasomal and lysosomal pathways; NEDD4 is also required for mGlu7-dependent MAPK signaling. Co-immunoprecipitation in HEK293 cells and rat neurons, ubiquitination assay, surface expression assay, endocytosis assay, MAPK signaling readout, siRNA knockdown eLife High 31373553
2020 NEDD4 promotes oligodendrocyte differentiation and developmental myelination by stabilizing VHL via K63-linked ubiquitination; the Daam2-VHL-NEDD4 axis governs OPC differentiation during development and remyelination after white matter injury. Conditional KO mouse models (Nedd4 KO), proteomic analysis of Daam2-VHL complex, K63-linked ubiquitination assay, myelination/remyelination assays, human MS lesion analysis Genes & development High 32792353
2016 LRAD3, a member of the LDL receptor family, activates NEDD4 E3 ligase activity via its intracellular PPxY motifs binding to the WW domains of NEDD4; binding to the terminal PPxY motif of LRAD3 is required to promote NEDD4 auto-ubiquitination and subsequent proteasomal degradation. Co-immunoprecipitation, in vitro ubiquitination (auto-ubiquitination) assay, PPxY mutagenesis, proteasome inhibitor experiments Biochemistry Medium 26854353
2024 Lactate inhibits NEDD4-mediated ubiquitination of Caspase-11 by inducing K33 lactylation of NEDD4, which impairs the interaction between NEDD4 and Caspase-11, thereby allowing Caspase-11 accumulation and promoting non-canonical pyroptosis in macrophages during acetaminophen-induced liver injury. Co-immunoprecipitation, ubiquitination assay, lactylation detection, site-directed mutagenesis (NEDD4 K33), macrophage pyroptosis assay, mouse APAP liver injury model International journal of biological sciences Medium 38385085
2022 NEDD4 ubiquitinates and promotes proteasomal degradation of NLRP3 by interacting with adaptor protein SF3A2, which bridges NEDD4 to NLRP3; this inhibits NLRP3 inflammasome activation and macrophage pyroptosis. Co-immunoprecipitation (NEDD4-SF3A2-NLRP3), Western blot for NLRP3 levels after NEDD4 overexpression/knockdown, pyroptosis assay, mouse MI/R model Cell communication and signaling Medium 36732831
2024 NEDD4-1 interacts with the PPTY motif of VDAC1 via its WW domain and catalyzes K48-linked ubiquitination of VDAC1, promoting its proteasomal degradation; hepatocyte-specific Nedd4-1 KO increases VDAC1 accumulation and oligomerization, worsening APAP-induced mitochondrial damage and liver injury. Co-immunoprecipitation, in vivo/in vitro ubiquitination assay (K48-linkage specific), hepatocyte-specific KO and overexpression mouse models, VDAC1 knockdown rescue experiments Acta pharmaceutica Sinica. B High 37139424
2021 NEDD4 is the E3 ubiquitin ligase for E-cadherin; N4BP3 acts as an adaptor that promotes NEDD4-mediated K48/K63-linked polyubiquitination and degradation of E-cadherin, driving breast cancer metastasis via EMT. Co-immunoprecipitation, in vitro ubiquitination assay, in vivo metastasis assay, N4BP3 depletion experiments Cancer letters Medium 36162713
2022 NEDD4 promotes TGFBR1 signaling by binding directly to TGF-β type I receptor (TGFBR1) and forming K27-linked ubiquitin at lysine 391, thereby enhancing TGF-β signal transduction and tumor cell migration in hepatocellular carcinoma. Co-immunoprecipitation, in vivo ubiquitination assay (K27-specific), NEDD4 knockdown with HCC migration/invasion assays, PDX model Oncogene Medium 35501461
2024 NEDD4 interacts with and ubiquitinates DMT1 (divalent metal transporter 1) at lysine residues 6, 69, and 277, facilitating DMT1 degradation and reducing iron accumulation/ferroptosis after intracerebral hemorrhage; NEDD4 overexpression alleviated ferroptosis and improved neurological outcomes. Co-immunoprecipitation, ubiquitination assay (site-directed mutagenesis of K6/K69/K277), lentiviral Nedd4 overexpression, ferroptosis markers (GPX4, MDA, iron content), mouse ICH model CNS neuroscience & therapeutics Medium 38634270
2024 NEDD4 catalyzes K48-linked ubiquitination of TAK1 at sites in TAK1, promoting its proteasomal degradation; THBS1 protects TAK1 from NEDD4-mediated ubiquitination by interacting with TAK1, and THBS1 silencing upregulates NEDD4 expression, leading to increased TAK1 degradation and necroptosis in trophoblasts. Co-immunoprecipitation, K48-specific ubiquitination assay, NEDD4 knockdown/overexpression, THBS1 silencing, mouse PE model Advanced science Medium 38569496
2023 NEDD4 binds to and mediates ubiquitination and proteasomal degradation of CSF1R in macrophages; IFN-I signaling increases NEDD4-mediated CSF1R ubiquitination, and USP18 impairs this by interrupting NEDD4 binding to CSF1R. Co-immunoprecipitation, in vitro ubiquitination assay, USP18 KO macrophage experiments, CSF1R protein stability assay Cell reports Medium 38100351
2021 NEDD4 triggers ubiquitination and proteasomal degradation of the transcription factor FOXA1; FOXA1 transcriptionally activates miR-340-5p which suppresses ATF1, creating a regulatory axis downstream of NEDD4 in colon cancer progression. Co-immunoprecipitation, ubiquitination assay, chromatin immunoprecipitation, luciferase reporter assay, in vivo xenograft model RNA biology Medium 33530829
2020 YOD1 (deubiquitinase) binds to and deubiquitinates NEDD4; YOD1 removes K63-linked polyubiquitin chains from NEDD4 and suppresses NEDD4-induced cell proliferation. Co-immunoprecipitation, deubiquitination assay, K63-specific ubiquitin chain analysis, cell proliferation assay with YOD1/NEDD4 overexpression Cellular physiology and biochemistry Medium 31916733
2023 NEDD4-1 ubiquitinates SR-BI at K500 and K508, promoting its degradation; hepatocyte lipocalin-2 (Lcn2) blocks this Nedd4-1-mediated SR-BI ubiquitination, improving HDL metabolism and reducing atherosclerosis in mice. Co-immunoprecipitation, ubiquitination assay (site-directed mutagenesis K500/K508), hepatocyte-specific Lcn2 KO and overexpression, Nedd4-1 KO mice, SR-BI K500A/K508A knock-in mice Developmental cell High 37863040
2024 GSK-3β phosphorylates PGC-1α at Thr295, creating a recognition motif for NEDD4-1, which then catalyzes ubiquitin-dependent proteasomal degradation of PGC-1α; mutation of Thr295 negates shikonin's suppressive effects on mitochondrial biogenesis and TNBC metastasis. Co-immunoprecipitation, ubiquitination assay, phosphorylation site mutagenesis (Thr295), LC-MS/MS identification of phosphorylation, in vivo TNBC metastasis model Journal of experimental & clinical cancer research Medium 38937832
2017 Adaptor protein Numb binds NEDD4-1 and regulates its E3 ligase activity and its association with PTEN, thereby controlling PTEN ubiquitination; Numb regulates cell proliferation and glucose metabolism in a PTEN-dependent manner. Co-immunoprecipitation (Numb-NEDD4-1 interaction), ubiquitination assay for PTEN, Numb knockdown with PTEN stability readout, cell proliferation and glucose metabolism assays Cell cycle Medium 28437168
2018 NEDD4 TV3 (a specific transcript variant) activates the NF-κB pathway through its association with the adaptor protein RIP, contributing to inflammation in keloid formation. Forced expression and selective knockdown of NEDD4 TV3, NF-κB reporter assay, co-immunoprecipitation with RIP, in vivo keloid mouse model The Journal of investigative dermatology Medium 30273597

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 NEDD4-1 is a proto-oncogenic ubiquitin ligase for PTEN. Cell 600 17218260
2020 Nedd4 ubiquitylates VDAC2/3 to suppress erastin-induced ferroptosis in melanoma. Nature communications 391 31974380
2001 Serum and glucocorticoid-regulated kinase modulates Nedd4-2-mediated inhibition of the epithelial Na+ channel. The Journal of biological chemistry 357 11696533
2000 Ubiquitination and endocytosis of plasma membrane proteins: role of Nedd4/Rsp5p family of ubiquitin-protein ligases. The Journal of membrane biology 302 10882424
2010 Nedd4 and Nedd4-2: closely related ubiquitin-protein ligases with distinct physiological functions. Cell death and differentiation 194 19557014
2007 The Nedd4-like family of E3 ubiquitin ligases and cancer. Cancer metastasis reviews 186 17726579
1999 Nedd4-like proteins: an emerging family of ubiquitin-protein ligases implicated in diverse cellular functions. Trends in cell biology 184 10322449
2000 Regulation of the epithelial Na+ channel by Nedd4 and ubiquitination. Kidney international 183 10720933
2007 Nedd4-2 catalyzes ubiquitination and degradation of cell surface ENaC. The Journal of biological chemistry 179 17502380
2008 Nedd4 mediates agonist-dependent ubiquitination, lysosomal targeting, and degradation of the beta2-adrenergic receptor. The Journal of biological chemistry 165 18544533
2008 The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization. Proceedings of the National Academy of Sciences of the United States of America 156 18562292
2002 Concerted action of ENaC, Nedd4-2, and Sgk1 in transepithelial Na(+) transport. American journal of physiology. Renal physiology 156 12167587
2014 NEDD4-2 (NEDD4L): the ubiquitin ligase for multiple membrane proteins. Gene 149 25433090
2011 Nedd4-mediated AMPA receptor ubiquitination regulates receptor turnover and trafficking. Journal of neurochemistry 141 21338354
2008 Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal secretion of Nedd4 family proteins. The Journal of biological chemistry 136 18819914
1997 cDNA cloning, expression analysis, and mapping of the mouse Nedd4 gene. Genomics 132 9073511
2014 NEDD4: The founding member of a family of ubiquitin-protein ligases. Gene 122 25527121
2021 FGFR3 Destabilizes PD-L1 via NEDD4 to Control T-cell-Mediated Bladder Cancer Immune Surveillance. Cancer research 110 34753771
2020 NEDD4 E3 ligase: Functions and mechanism in human cancer. Seminars in cancer biology 101 32171886
2007 The Nedd4-binding partner 1 (N4BP1) protein is an inhibitor of the E3 ligase Itch. Proceedings of the National Academy of Sciences of the United States of America 98 17592138
2015 Molecular functions of NEDD4 E3 ubiquitin ligases in cancer. Biochimica et biophysica acta 88 26116757
1999 mGrb10 interacts with Nedd4. The Journal of biological chemistry 88 10446181
2020 E3 Ubiquitin ligase NEDD4 family‑regulatory network in cardiovascular disease. International journal of biological sciences 86 33110392
2019 The many substrates and functions of NEDD4-1. Cell death & disease 85 31787758
2019 NEDD4 and NEDD4L regulate Wnt signalling and intestinal stem cell priming by degrading LGR5 receptor. The EMBO journal 82 31867777
2018 NEDD4 Is Involved in Inflammation Development during Keloid Formation. The Journal of investigative dermatology 79 30273597
2014 Regulation of Mdm2 protein stability and the p53 response by NEDD4-1 E3 ligase. Oncogene 79 24413081
2015 NEDD4-mediated HSF1 degradation underlies α-synucleinopathy. Human molecular genetics 77 26503960
2014 Impeded Nedd4-1-mediated Ras degradation underlies Ras-driven tumorigenesis. Cell reports 73 24746824
2011 Nedd4-1 binds and ubiquitylates activated FGFR1 to control its endocytosis and function. The EMBO journal 73 21765395
2010 FoxM1B regulates NEDD4-1 expression, leading to cellular transformation and full malignant phenotype in immortalized human astrocytes. Cancer research 71 20332230
2015 Nedd4-induced monoubiquitination of IRS-2 enhances IGF signalling and mitogenic activity. Nature communications 69 25879670
2004 The kinase Grk2 regulates Nedd4/Nedd4-2-dependent control of epithelial Na+ channels. Proceedings of the National Academy of Sciences of the United States of America 69 15284439
2003 The role of Nedd4/Nedd4-like dependant ubiquitylation in epithelial transport processes. Pflugers Archiv : European journal of physiology 68 12698368
2017 Allosteric auto-inhibition and activation of the Nedd4 family E3 ligase Itch. EMBO reports 64 28747490
2018 Physiological Functions of Nedd4-2: Lessons from Knockout Mouse Models. Trends in biochemical sciences 63 30056838
2020 Auto-ubiquitination of NEDD4-1 Recruits USP13 to Facilitate Autophagy through Deubiquitinating VPS34. Cell reports 62 32101753
2010 Nedd4-1 and beta-arrestin-1 are key regulators of Na+/H+ exchanger 1 ubiquitylation, endocytosis, and function. The Journal of biological chemistry 62 20855896
2017 Epilepsy-associated gene Nedd4-2 mediates neuronal activity and seizure susceptibility through AMPA receptors. PLoS genetics 59 28212375
2023 m6A eraser FTO impairs gemcitabine resistance in pancreatic cancer through influencing NEDD4 mRNA stability by regulating the PTEN/PI3K/AKT pathway. Journal of experimental & clinical cancer research : CR 58 37605223
2015 NEDD4 controls intestinal stem cell homeostasis by regulating the Hippo signalling pathway. Nature communications 55 25692647
2018 Nedd4-Binding Protein 1 and TNFAIP3-Interacting Protein 1 Control MHC-1 Display in Neuroblastoma. Cancer research 54 30213788
2008 Expression of NEDD4-1, a PTEN regulator, in gastric and colorectal carcinomas. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 54 19024597
2012 Nedd4 and Nedd4-2: ubiquitin ligases at work in the neuron. The international journal of biochemistry & cell biology 51 23262292
2018 A Tyrosine Switch on NEDD4-2 E3 Ligase Transmits GPCR Inflammatory Signaling. Cell reports 49 30232011
2024 NEDD4 lactylation promotes APAP induced liver injury through Caspase11 dependent non-canonical pyroptosis. International journal of biological sciences 48 38385085
2019 Nedd4 E3 ligase and beta-arrestins regulate ubiquitination, trafficking, and stability of the mGlu7 receptor. eLife 46 31373553
2017 Ubiquitylation-dependent oligomerization regulates activity of Nedd4 ligases. The EMBO journal 46 28069708
2017 H3 ubiquitination by NEDD4 regulates H3 acetylation and tumorigenesis. Nature communications 42 28300060
2005 Impact of Nedd4 proteins and serum and glucocorticoid-induced kinases on epithelial Na+ transport in the distal nephron. Journal of the American Society of Nephrology : JASN 42 16192418
2021 14-3-3-protein regulates Nedd4-2 by modulating interactions between HECT and WW domains. Communications biology 41 34294877
2015 Nedd4 E3 ubiquitin ligase promotes cell proliferation and autophagy. Cell proliferation 41 25809873
2017 NEDD4 promotes cell growth and migration via PTEN/PI3K/AKT signaling in hepatocellular carcinoma. Oncology letters 40 28928809
2017 Regulation of PTEN degradation and NEDD4-1 E3 ligase activity by Numb. Cell cycle (Georgetown, Tex.) 39 28437168
2017 NDFIP allows NEDD4/NEDD4L-induced AQP2 ubiquitination and degradation. PloS one 39 28931009
2015 NEDD4-2 and salt-sensitive hypertension. Current opinion in nephrology and hypertension 38 25602517
2009 Nedd4 mediates ErbB4 JM-a/CYT-1 ICD ubiquitination and degradation in MDCK II cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 19193720
2023 NEDD4 ameliorates myocardial reperfusion injury by preventing macrophages pyroptosis. Cell communication and signaling : CCS 35 36732831
2022 The Roles of NEDD4 Subfamily of HECT E3 Ubiquitin Ligases in Neurodevelopment and Neurodegeneration. International journal of molecular sciences 31 35409239
2021 NEDD4 triggers FOXA1 ubiquitination and promotes colon cancer progression under microRNA-340-5p suppression and ATF1 upregulation. RNA biology 31 33530829
2019 Comparative analysis of the catalytic regulation of NEDD4-1 and WWP2 ubiquitin ligases. The Journal of biological chemistry 31 31578285
2019 The NEDD4-1 E3 ubiquitin ligase: A potential molecular target for bortezomib sensitivity in multiple myeloma. International journal of cancer 30 31390487
2018 Kir5.1 regulates Nedd4-2-mediated ubiquitination of Kir4.1 in distal nephron. American journal of physiology. Renal physiology 30 29897283
2013 NEDD4-1 regulates migration and invasion of glioma cells through CNrasGEF ubiquitination in vitro. PloS one 30 24340059
2023 Nedd4-2 up-regulation is associated with ACE2 ubiquitination in hypertension. Cardiovascular research 29 37161607
2020 The Daam2-VHL-Nedd4 axis governs developmental and regenerative oligodendrocyte differentiation. Genes & development 29 32792353
2014 NEDD4 controls the expression of GUCD1, a protein upregulated in proliferating liver cells. Cell cycle (Georgetown, Tex.) 29 24743017
2024 Thrombospondin-1 Regulates Trophoblast Necroptosis via NEDD4-Mediated Ubiquitination of TAK1 in Preeclampsia. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 28 38569496
2024 Shikonin blocks CAF-induced TNBC metastasis by suppressing mitochondrial biogenesis through GSK-3β/NEDD4-1 mediated phosphorylation-dependent degradation of PGC-1α. Journal of experimental & clinical cancer research : CR 28 38937832
2017 NEDD4 controls spermatogonial stem cell homeostasis and stress response by regulating messenger ribonucleoprotein complexes. Nature communications 28 28585553
2021 microRNA-454-mediated NEDD4-2/TrkA/cAMP axis in heart failure: Mechanisms and cardioprotective implications. Journal of cellular and molecular medicine 27 33949117
2017 NEDD4-1 protects against ischaemia/reperfusion-induced cardiomyocyte apoptosis via the PI3K/Akt pathway. Apoptosis : an international journal on programmed cell death 27 27837380
2018 The Role of Intercalated Cell Nedd4-2 in BP Regulation, Ion Transport, and Transporter Expression. Journal of the American Society of Nephrology : JASN 26 29773687
2016 Nedd4-2 haploinsufficiency causes hyperactivity and increased sensitivity to inflammatory stimuli. Scientific reports 26 27604420
2014 Crosstalk between kinases and Nedd4 family ubiquitin ligases. Molecular bioSystems 26 24457516
2007 GRK2 interacts with and phosphorylates Nedd4 and Nedd4-2. Biochemical and biophysical research communications 25 17544362
2005 The ubiquitin-protein ligases Nedd4 and Nedd4-2 show similar ubiquitin-conjugating enzyme specificities. The international journal of biochemistry & cell biology 25 16337426
2021 Obestatin signalling counteracts glucocorticoid-induced skeletal muscle atrophy via NEDD4/KLF15 axis. Journal of cachexia, sarcopenia and muscle 24 33687156
2023 The E3 ubiquitin ligase NEDD4-1 protects against acetaminophen-induced liver injury by targeting VDAC1 for degradation. Acta pharmaceutica Sinica. B 23 37139424
2019 PLPP/CIN-mediated NEDD4-2 S448 dephosphorylation regulates neuronal excitability via GluA1 ubiquitination. Cell death & disease 23 31320629
2015 Cell autonomous roles of Nedd4 in craniofacial bone formation. Developmental biology 23 26681395
2022 The Role of NEDD4 E3 Ubiquitin-Protein Ligases in Parkinson's Disease. Genes 22 35328067
2022 N4BP3 promotes breast cancer metastasis via NEDD4-mediated E-cadherin ubiquitination and degradation. Cancer letters 22 36162713
2022 Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer. International journal of molecular sciences 22 36293239
2019 LINC01198 promotes proliferation and temozolomide resistance in a NEDD4-1-dependent manner, repressing PTEN expression in glioma. Aging 22 31469661
2024 ECHDC2 inhibits the proliferation of gastric cancer cells by binding with NEDD4 to degrade MCCC2 and reduce aerobic glycolysis. Molecular medicine (Cambridge, Mass.) 21 38783226
2023 NEDD4 E3 ubiquitin ligases: Promising biomarkers and therapeutic targets for cancer. Biochemical pharmacology 21 37307883
2023 Reprogramming of tumor-associated macrophages via NEDD4-mediated CSF1R degradation by targeting USP18. Cell reports 21 38100351
2021 NEDD4 regulates ubiquitination and stability of the cell adhesion molecule IGPR-1 via lysosomal pathway. Journal of biomedical science 21 33962630
2020 YOD1 Deubiquitinates NEDD4 Involved in the Hippo Signaling Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 21 31916733
2020 Piezo2 channel in nodose ganglia neurons is essential in controlling hypertension in a pathway regulated directly by Nedd4-2. Pharmacological research 21 33352230
2018 NEDD4 promotes cell growth and motility in hepatocellular carcinoma. Cell cycle (Georgetown, Tex.) 21 29480061
2016 Regulation of Itch and Nedd4 E3 Ligase Activity and Degradation by LRAD3. Biochemistry 21 26854353
2020 An outlined review for the role of Nedd4-1 and Nedd4-2 in lung disorders. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 32092816
2017 PKC/Nedd4-2 Signaling Pathway Regulates the Cell Surface Expression of Drug Transporter hOAT1. Drug metabolism and disposition: the biological fate of chemicals 20 28572241
2015 PTEN and NEDD4 in Human Breast Carcinoma. Pathology oncology research : POR 20 26276352
2008 Cbl- and Nedd4-family ubiquitin ligases: balancing tolerance and immunity. Immunologic research 20 18827983
2024 DMT1 ubiquitination by Nedd4 protects against ferroptosis after intracerebral hemorrhage. CNS neuroscience & therapeutics 19 38634270
2023 Hepatocytic lipocalin-2 controls HDL metabolism and atherosclerosis via Nedd4-1-SR-BI axis in mice. Developmental cell 19 37863040
2022 Insufficient ablation induces E3-ligase Nedd4 to promote hepatocellular carcinoma progression by tuning TGF-β signaling. Oncogene 18 35501461

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