Affinage

SMURF2

E3 ubiquitin-protein ligase SMURF2 · UniProt Q9HAU4

Length
748 aa
Mass
86.2 kDa
Annotated
2026-06-10
100 papers in source corpus 55 papers cited in narrative 53 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

SMURF2 is a C2-WW-HECT domain E3 ubiquitin ligase that governs the strength and duration of TGFβ/BMP signaling and a broad program of cell-cycle, chromatin, and stress-response events through substrate-specific ubiquitination (PMID:11163210, PMID:11016919, PMID:11158580). Its catalytic activity is held in check by an intramolecular C2–HECT interaction that occludes the catalytic cysteine and blocks ubiquitin-thioester formation; this autoinhibition is relieved when adaptor proteins such as Smad7—and, by a shared mechanism, Dishevelled—bind the HECT domain, while the Smad7 N-terminal domain further stimulates activity by recruiting the E2 UbcH7 into a suboptimal E2-binding pocket (PMID:16061177, PMID:17719543, PMID:32392721). Substrate selection is achieved through its WW domains, which read PPxY/PY motifs via an expanded recognition surface that engages both the core PY motif and a C-terminal tail (PMID:16641086, PMID:24121673, PMID:24803334). In the TGFβ axis, the Smad7-SMURF2 complex is exported to the activated receptor and degrades both receptor and Smad7 (PMID:11163210), SMURF2 ubiquitinates R-Smads (degradative for Smad1/2, multi-monoubiquitination of Smad3 that blocks complex formation) (PMID:11016919, PMID:11158580, PMID:22045334), and clears the co-repressor SnoN (PMID:11389444); it also restrains BMP-driven Smad1/5 signaling (PMID:33298874). Beyond this core pathway, SMURF2 controls mitotic fidelity by stabilizing Mad2 to enforce the spindle assembly checkpoint and by protecting Topoisomerase IIα to allow catenane resolution (PMID:18852296, PMID:28611047), and it shapes the chromatin and DNA-damage landscape by degrading RNF20 to set H2B-ubiquitination/H3K4-H3K79 methylation marks at double-strand breaks (PMID:22231558). SMURF2 drives telomere-attrition-triggered senescence—a function genetically linked to tumor suppression in knockout mice that develop B-cell lymphoma (PMID:15574587, PMID:22552287)—and acts as a ferroptosis modulator by degrading the lipid-peroxide defense enzyme GSTP1 (PMID:38016474). Its own abundance and activity are tuned by phosphorylation (Akt-driven degradation; Thr249-dependent activation), sumoylation by PIAS3/Ubc9 at K26/K369, USP15-mediated deubiquitination at K734, and competitive adaptor exchange between Smad7 and RNF11 (PMID:24961731, PMID:35017630, PMID:26679521, PMID:26435193, PMID:28292929). Notably, SMURF2 acts as a stabilizer as well as a degrader for a subset of clients (EGFR, NEDD9, Topo IIα, CNKSR2), often via non-degradative ubiquitination (PMID:21750651, PMID:32669362, PMID:20825672, PMID:28611047, PMID:29534682).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 High

    Established SMURF2's foundational role: how is TGFβ receptor signaling terminated? It works as a HECT E3 that, via the Smad7 adaptor, targets the activated receptor for degradation, and it directly degrades receptor-regulated Smads.

    Evidence Co-IP, subcellular fractionation, receptor degradation and ubiquitination assays; yeast two-hybrid and Xenopus overexpression

    PMID:11016919 PMID:11158580 PMID:11163210

    Open questions at the time
    • Did not resolve how SMURF2 catalytic activity is regulated
    • Smad4 selectivity rationale unaddressed at structural level
  2. 2001 High

    Defined SMURF2 substrate-recruitment logic: TGFβ induces a Smad2-SMURF2 complex via Smad2 PPxY–WW interaction that degrades the co-repressor SnoN, extending SMURF2's reach to transcriptional regulators.

    Evidence Co-IP, in vivo ubiquitination, proteasome inhibition, domain mapping

    PMID:11389444

    Open questions at the time
    • WW-domain structural basis of PY recognition not yet defined
    • In vivo relevance unaddressed
  3. 2005 High

    Explained how the Smad7 adaptor activates SMURF2 catalysis: the Smad7 NTD recruits UbcH7 to a suboptimal E2 pocket in the HECT domain, defined by a 2.1 Å crystal structure.

    Evidence X-ray crystallography, in vitro ubiquitination, site-directed mutagenesis

    PMID:16061177

    Open questions at the time
    • Did not explain basal autoinhibition of full-length enzyme
  4. 2006 High

    Resolved the molecular basis of substrate specificity: the WW3 domain recognizes both the PY core and an extended PY-tail, an expanded recognition surface.

    Evidence NMR solution structure of WW3–Smad7 PY peptide complex with binding measurements

    PMID:16641086

    Open questions at the time
    • Generalizability of PY-tail recognition to other substrates untested
  5. 2007 High

    Defined the autoinhibition mechanism: an intramolecular C2–HECT interaction near the catalytic cysteine blocks ubiquitin thioester formation and is antagonized by Smad7 binding.

    Evidence NMR, in vitro ubiquitination, domain deletion/mutagenesis, cell-based stability assays

    PMID:17719543

    Open questions at the time
    • Full-length enzyme conformational dynamics not resolved structurally
  6. 2007 High

    Extended SMURF2 into neuronal polarity: it ubiquitinates inactive Rap1B for degradation, restricting it to the future axon, with mPar3/Kinesin-2 providing spatial targeting.

    Evidence Neuronal RNAi, in vivo ubiquitination, localization imaging, rescue; co-IP and dominant-negative interference

    PMID:17318188 PMID:17906294

    Open questions at the time
    • mPar3–Kinesin-2 link is single-lab Medium-confidence
    • Mechanism of Rap1B activity-state selectivity unclear
  7. 2004 High

    Linked SMURF2 to senescence and aging: telomere attrition upregulates SMURF2, and its overexpression induces senescence via Rb/p53 through an activity distinct from canonical E3 ligase function.

    Evidence Retroviral overexpression, BrdU, SA-β-gal, E3-dead mutant controls

    PMID:15574587

    Open questions at the time
    • The non-E3 senescence activity remains molecularly undefined
    • p21-independence mechanism unresolved
  8. 2008 High

    Established SMURF2 as a mitotic regulator: it localizes to centrosome/midbody/centromeres and enforces the spindle assembly checkpoint by stabilizing Mad2, with Cdc20-silencing epistasis confirming the SAC role.

    Evidence siRNA, immunofluorescence, flow cytometry, co-IP, nocodazole arrest, Cdc20 rescue

    PMID:18852296

    Open questions at the time
    • Direct ubiquitination linkage on Mad2 vs indirect protection not fully separated
  9. 2008 High

    Showed SMURF2 controls its paralog: it degrades Smurf1 unidirectionally, and loss of this control enhances breast cancer migration and bone metastasis.

    Evidence Co-IP, in vivo ubiquitination, siRNA, migration/invasion, in vivo metastasis model

    PMID:18927080

    Open questions at the time
    • Structural basis of unidirectional degradation not addressed
  10. 2010 High

    Connected SMURF2 to Wnt signaling: it ubiquitinates Axin at Lys505 to promote degradation, modulating β-catenin/Tcf activity.

    Evidence Co-IP, in vitro/in vivo ubiquitination, MS site mapping, shRNA, reporter, K505R mutant

    PMID:20858899

    Open questions at the time
    • In vivo physiological role in Wnt signaling not established
  11. 2011 High

    Refined the Smad3 mechanism in vivo: SMURF2 multi-monoubiquitinates Smad3 to block complex formation rather than degrading it, with T179 phosphorylation enhancing the interaction.

    Evidence Smurf2 KO mice, primary cells, in vivo ubiquitination, site mapping, phospho-mutants

    PMID:22045334

    Open questions at the time
    • Switch between mono- and poly-ubiquitination determinants unclear
  12. 2012 High

    Tied SMURF2 to chromatin and genome stability: it degrades RNF20, setting H2B-Ub/H3K4me3/H3K79me marks, co-localizes at DSBs, and its loss causes genomic instability and cancer susceptibility.

    Evidence Smurf2 KO mice, co-IP, IF co-localization, histone modification and DDR assays

    PMID:22231558 PMID:22552287

    Open questions at the time
    • Direct chromatin recruitment mechanism at breaks not defined
  13. 2015 High

    Revealed adaptor competition and post-translational tuning: RNF11 competes with Smad7 to activate SMURF2 on endomembranes, while sumoylation (PIAS3/Ubc9), USP15 deubiquitination, and Akt phosphorylation set its activity and abundance.

    Evidence In vitro reconstitution and competition, co-IP, sumoylation/ubiquitination site mapping, reporter assays

    PMID:24961731 PMID:26435193 PMID:26679521 PMID:28292929

    Open questions at the time
    • RNF11 finding is High; sumoylation/USP15/Akt are single-lab Medium
    • Integration of these modifications in vivo unresolved
  14. 2016 High

    Expanded the substrate and innate-immunity repertoire: SMURF2 degrades VISA/MAVS to dampen type I IFN signaling and targets YY1, Id1/3, EZH2, and others, broadening its regulatory scope.

    Evidence Co-IP, linkage-specific in vivo ubiquitination, catalytic mutants, KO/KD with functional readouts

    PMID:21933340 PMID:23526793 PMID:24121673 PMID:24729608 PMID:24803334

    Open questions at the time
    • VISA/YY1 High-confidence; EZH2/Id1-3 single-lab Medium
    • Substrate selection rules across this set undefined
  15. 2020 High

    Defined a non-degradative stabilizing mode: SMURF2-UBCH5 polyubiquitinates mutant EGFR at four lysines to retain it at the membrane and block lysosomal sorting, protecting it from degradation.

    Evidence In vitro/in vivo ubiquitination, MS site mapping, superresolution imaging, acetyl-mimic mutant, siRNA

    PMID:21750651 PMID:32669362

    Open questions at the time
    • Determinants distinguishing stabilizing vs degradative chains on a given substrate unclear
  16. 2022 Medium

    Linked SMURF2 activity to phosphorylation control and cancer stemness: Thr249 phosphorylation activates the ligase, and its loss stabilizes TGFBR1 to enhance glioma stem-cell tumorigenicity.

    Evidence T249A phospho-mutant, TGFBR1 stability and GSC sphere/tumor assays, knockdown rescue

    PMID:35017630

    Open questions at the time
    • Upstream Thr249 kinase identity not established
    • Single-lab
  17. 2023 High

    Placed SMURF2 in ferroptosis defense: it degrades GSTP1, a GPX4/FSP1-independent lipid-peroxide detoxifier, making the SMURF2/GSTP1 axis a determinant of ferroptosis drug sensitivity.

    Evidence Proteomics, co-IP, in vivo ubiquitination, GSTP1 catalytic assays, in vitro/in vivo drug sensitivity

    PMID:38016474

    Open questions at the time
    • Trigger that activates SMURF2 toward GSTP1 early in ferroptosis unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single ligase chooses between degradative polyubiquitination, attenuating mono-ubiquitination, and outright substrate stabilization for its many clients—and how upstream signals coordinate this choice spatially—remains unresolved.
  • No unifying model for chain-type/outcome selection across substrates
  • Spatial (nuclear vs cytoplasmic vs endomembrane) control of substrate choice incomplete
  • Non-E3 senescence activity remains molecularly undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 7 GO:0140096 catalytic activity, acting on a protein 6 GO:0016874 ligase activity 5 GO:0098772 molecular function regulator activity 4
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0000228 nuclear chromosome 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-1640170 Cell Cycle 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-168256 Immune System 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-73894 DNA Repair 2 R-HSA-4839726 Chromatin organization 1
Partners
DVLEGFRPIAS3RNF11SMAD2SMAD3SMAD7USP15
Complex memberships
SMURF2-UBCH5 (UbcH5) E3:E2 complexSmad7-SMURF2 E3 ligase complex

Evidence

Reading pass · 53 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Smurf2 is a C2-WW-HECT domain E3 ubiquitin ligase that constitutively associates with Smad7; this Smad7-Smurf2 complex is exported from the nucleus and recruited to the activated TGFβ receptor, where it targets both the receptor and Smad7 for degradation via proteasomal and lysosomal pathways. Smad7 functions as an adaptor in this E3 ligase complex. Co-immunoprecipitation, subcellular fractionation, receptor degradation assays, dominant-negative and RNAi expression studies Molecular cell High 11163210
2000 Smurf2 selectively interacts with receptor-regulated Smads (Smad1, Smad2, Smad3 but not Smad4) and preferentially targets Smad1 and Smad2 for ubiquitination and proteasome-mediated degradation; HECT catalytic activity is required. Smurf2 shows higher binding affinity to activated (phosphorylated) Smad2 upon TGF-β stimulation. Yeast two-hybrid, in vitro binding assays, in vivo ubiquitination assays, proteasome inhibitor experiments, Xenopus embryo overexpression The Journal of biological chemistry / Proceedings of the National Academy of Sciences High 11016919 11158580
2001 TGF-β stimulation induces assembly of a Smad2-Smurf2 ubiquitin ligase complex via interaction of the Smad2 proline-rich PPXY motif with WW domains of Smurf2; this complex associates with the transcriptional co-repressor SnoN and targets it for ubiquitin-mediated proteasomal degradation. Co-immunoprecipitation, in vivo ubiquitination assay, proteasome inhibitor experiments, domain mapping Nature cell biology High 11389444
2005 The N-terminal domain (NTD) of Smad7 stimulates Smurf2 ubiquitin ligase activity by recruiting the E2 enzyme UbcH7 to the HECT domain. A 2.1 Å crystal structure of the Smurf2 HECT domain revealed a suboptimal E2 binding pocket; mutagenesis to optimize this pocket generated a constitutively active HECT domain that inhibits TGFβ signaling independently of Smad7. X-ray crystallography (2.1 Å), in vitro ubiquitination assays, site-directed mutagenesis Molecular cell High 16061177
2007 An intramolecular interaction between the C2 and HECT domains of Smurf2 autoinhibits its ubiquitin ligase activity by binding near the catalytic cysteine and interfering with ubiquitin thioester formation; Smad7 binding to the HECT domain antagonizes this inhibitory C2-HECT interaction to activate Smurf2. NMR spectroscopy, in vitro ubiquitination assays, domain deletion/mutagenesis, cell-based stability assays Cell High 17719543
2006 NMR solution structure of the Smurf2 WW3 domain in complex with the Smad7 PY motif peptide revealed that WW3 (which has Phe instead of the canonical Trp) binds both the core PY motif and six C-terminal residues (PY-tail), defining an expanded WW domain recognition surface that provides substrate specificity. NMR spectroscopy (solution structure determination), binding affinity measurements The Journal of biological chemistry High 16641086
2007 Smurf2 ubiquitinates inactive Rap1B and initiates its proteasomal degradation in hippocampal neurons; this restricts Rap1B to the tip of a single neurite (the future axon), establishing neuronal polarity. Smurf1 and Smurf2 have distinct roles: Smurf1 regulates Rho/neurite growth and Smurf2 regulates Rap1B/polarity. RNAi knockdown in neurons, in vivo ubiquitination assay, fluorescence imaging of Rap1B localization, rescue experiments The EMBO journal High 17318188
2007 mPar3 links Smurf2 to Kinesin-2 and is required to localize Smurf2 to neuronal growth cones; disruption of mPar3–Kinesin-2 or mPar3–Smurf2 interactions prevents restriction of Rap1B to the axon and abolishes neuronal polarity. Co-immunoprecipitation, RNAi knockdown, dominant-negative interference, fluorescence localization in neurons The Journal of biological chemistry Medium 17906294
2004 Smurf2 up-regulation is a specific consequence of telomere attrition in human fibroblasts, and ectopic Smurf2 expression at physiological levels is sufficient to induce senescence. The senescence-inducing function requires a novel activity distinct from Smurf2's E3 ligase activity, and involves recruitment of the Rb and p53 pathways; p21 is elevated but Smurf2-induced senescence is p21-independent. Retroviral overexpression, BrdU incorporation, senescence-associated β-galactosidase staining, gene expression analysis, E3-dead mutant rescue Genes & development High 15574587
2008 Smurf2 localizes to the centrosome, mitotic midbody, and centromeres. Smurf2 depletion causes misaligned/lagging chromosomes, premature anaphase, and defective cytokinesis. Smurf2 is required for the spindle assembly checkpoint (SAC): its inactivation leads to enhanced polyubiquitination and degradation of Mad2, mislocalizing Mad2 and preventing prometaphase arrest; silencing Cdc20 in Smurf2-depleted cells rescues cyclin B and securin accumulation. siRNA knockdown, immunofluorescence localization, flow cytometry, co-immunoprecipitation, nocodazole arrest assays, epistasis (Cdc20 silencing rescue) The Journal of cell biology High 18852296
2008 Smurf2 mediates ubiquitin-dependent degradation of Smurf1; Smurf2 interacts with Smurf1 and induces its ubiquitination and proteasomal degradation, whereas Smurf1 does not reciprocally degrade Smurf2. Knockdown of Smurf2 in breast cancer cells increases Smurf1 protein and enhances cell migration and bone metastasis. Co-immunoprecipitation, in vivo ubiquitination assay, siRNA knockdown, migration/invasion assays, in vivo bone metastasis model The Journal of biological chemistry High 18927080
2010 Smurf2 is an E3 ubiquitin ligase for Axin; it interacts with Axin, promotes its ubiquitination specifically at Lys505 (identified by mass spectrometry), and targets it for proteasomal degradation. Knockdown of endogenous Smurf2 increases endogenous Axin levels and reduces β-catenin/Tcf reporter activity. Co-immunoprecipitation, in vitro/in vivo ubiquitination assay, mass spectrometry, shRNA knockdown, luciferase reporter assay, K505R mutant resistance experiment The Journal of biological chemistry High 20858899
2011 In vivo (Smurf2 knockout mice), Smurf2 induces multiple mono-ubiquitination of Smad3 at MH2 domain lysine residues rather than polyubiquitination/degradation; this mono-ubiquitination inhibits Smad3 complex formation and attenuates TGF-β signaling. Phosphorylation of Smad3 at T179 enhances Smurf2-Smad3 interaction and Smad3 ubiquitination. Smurf2 knockout mouse generation, primary MEF/dermal fibroblast assays, in vivo ubiquitination assays, site mapping, phosphorylation-deficient mutant studies The EMBO journal High 22045334
2012 Smurf2 targets RNF20 for proteasomal degradation, thereby regulating monoubiquitination of histone H2B and trimethylation of H3K4 and H3K79. Smurf2 and RNF20 co-localize at γ-H2AX foci of double-strand DNA breaks. Smurf2 knockout mice show dysregulated DNA damage response, genomic instability, and increased cancer susceptibility. Smurf2 knockout mouse model, co-immunoprecipitation, immunofluorescence co-localization, histone modification assays, proteasome inhibitor experiments Nature medicine High 22231558
2011 Smurf2 mediates ubiquitination and degradation of Id1 and Id3 in senescent cells; Smurf2-mediated ubiquitination of Id1 (and its consequent degradation) is the mechanism by which Smurf2 up-regulates p16 expression during senescence. Co-immunoprecipitation, in vivo ubiquitination assay, siRNA knockdown, p16 reporter assays Aging cell Medium 21933340
2013 Smurf2 is the E3 ubiquitin ligase responsible for polyubiquitination and proteasomal degradation of EZH2 in human mesenchymal stem cells, which is required for neuron differentiation; EZH2 degradation by Smurf2 enables PPARγ expression to drive differentiation. Co-immunoprecipitation, in vivo ubiquitination assay, siRNA/shRNA knockdown, ChIP-on-chip, gene microarray, in vivo stroke model EMBO molecular medicine Medium 23526793
2013 Smurf2 interacts with VISA/MAVS and targets it for K48-linked polyubiquitination and proteasomal degradation, negatively regulating virus-triggered type I IFN signaling. The E3 ligase activity of Smurf2 (C716A mutant is inactive) is required for this negative regulation. Co-immunoprecipitation, in vivo ubiquitination assay (K48-linkage specific), Smurf2 KO/KD experiments, IFN-β reporter assays, C716A catalytic mutant Journal of immunology High 24729608
2013 Smurf2 mediates ubiquitination and degradation of YY1; Smurf2 interacts with YY1 via the PPxY motif of YY1, induces its polyubiquitination, and shortens YY1 half-life, thereby reducing YY1-mediated transcriptional activation. In B-cell lymphoma context, Smurf2 deficiency enhances YY1-mediated transactivation of c-Myc. Co-immunoprecipitation, in vivo ubiquitination assay, half-life measurement, PPxY mutant analysis, Smurf2 KO mouse model, luciferase reporter assay Nature communications / Biochimica et biophysica acta High 24121673 24803334
2014 Smurf2 forms an active E3:E2 complex with UBCH5 that maintains KRAS protein stability by mediating K48-linked monoubiquitination of UBCH5 at K144. This SMURF2:UBCH5 complex promotes degradation of β-TrCP1, an E3 ligase that itself degrades KRAS; loss of SMURF2 accumulates β-TrCP1 leading to KRAS degradation. siRNA/shRNA knockdown, overexpression rescue, in vivo ubiquitination assay, protein half-life measurements, domain mutagenesis (P residues in UBCH5) Neoplasia Medium 24709419
2014 Akt phosphorylates Smurf2 and promotes ubiquitin/proteasome-mediated degradation of Smurf2 itself, thereby increasing Runx2 protein stability and transcriptional activity. This establishes an Akt→Smurf2→Runx2 axis regulating osteoblast differentiation. Co-immunoprecipitation, phosphorylation assays, ubiquitination assays, Western blot, overexpression/knockdown experiments The FEBS journal Medium 24961731
2015 Smurf2 is sumoylated by the SUMO E2 enzyme Ubc9 and SUMO E3 ligase PIAS3 at Lys26 and Lys369; sumoylation enhances Smurf2's ability to degrade the TGFβ receptor and suppresses TGFβ-induced EMT. PIAS3 associates with Smurf2 and promotes its sumoylation. Co-immunoprecipitation, sumoylation assays, site-directed mutagenesis (K26R/K369R), 3D organoid EMT assay, siRNA knockdown Cell death and differentiation Medium 26679521
2015 USP15 deubiquitinates SMURF2 at Lys734 (a residue required for catalytic activity), thereby enhancing SMURF2's E3 ligase activity and increasing TGFβ receptor stability and downstream signaling. USP15 and SMURF2 form a regulatory axis within the TGFβ pathway. Co-immunoprecipitation, proteomic/mass spectrometry analysis of ubiquitination sites, in vivo ubiquitination assays, TGFβ pathway reporter assays Scientific reports Medium 26435193
2009 Ectopically expressed Smurf2 in chondrocytes interacts with GSK-3β, induces its ubiquitination and proteasomal degradation, and thereby upregulates β-catenin levels, activating articular chondrocyte maturation. Immunoprecipitation, ubiquitination assay, Col2a1-Smurf2 transgenic mouse ex vivo chondrocytes, Western blot Experimental cell research Medium 19481076
2010 Smurf2 physically associates with NEDD9/HEF1 and is required for NEDD9 protein stability by protecting it from polyubiquitination and proteasomal degradation; Smurf2 depletion reduces NEDD9 levels, prevents Aurora A activation at the G2/M boundary, and causes mitotic entry delay. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, Aurora A kinase activity assays, flow cytometry Cell division Medium 20825672
2016 AIMP2/p38, upon TGF-β-induced phosphorylation at S156 and nuclear translocation, binds Smurf2 in the nucleus to enhance ubiquitination of FBP (FUBP1). AIMP2 also inhibits nuclear export of Smurf2 to sustain TGFβ tumor-suppressive signaling. An oncogenic AIMP2 mutation abrogates this nuclear interaction with Smurf2. Co-immunoprecipitation, in vivo ubiquitination assays, subcellular fractionation, domain mutagenesis, in vivo tumor formation assays Cancer research Medium 27197155
2015 TRAF4 recruits SMURF2 to the IL-25 receptor complex; TRAF4-SMURF2 mediates degradation of DAZAP2 (an IL-25R inhibitory molecule), enabling ACT1 recruitment to IL-25R and IL-25 signaling. This is a critical initiating event for IL-25-driven type 2 allergic responses. Co-immunoprecipitation, ubiquitination assays, Traf4 knockout mouse model, IL-25 signaling assays, siRNA knockdown Journal of immunology Medium 25681341
2017 Smurf2 physically interacts with Topoisomerase IIα (Topo IIα), modifies its ubiquitination status to protect it from proteasomal degradation (stabilizing rather than degrading), and is a physiologic regulator of Topo IIα levels. Smurf2-depleted cells cannot resolve DNA catenanes and form pathological chromatin bridges during mitosis. Co-immunoprecipitation, in vivo ubiquitination assays, siRNA knockdown, chromosomal bridge quantification, Topo IIα rescue experiments Cancer research Medium 28611047
2017 SMURF2 regulates RANKL expression in osteoblasts by disrupting the interaction between SMAD3 and the vitamin D receptor through altering SMAD3 ubiquitination; Smurf2-deficient mice exhibit severe osteoporosis with increased osteoclast numbers driven by osteoblast-elevated RANKL. Osteoblast-selective Smurf2 deletion recapitulates the full osteoporosis phenotype. Conditional/germline knockout mouse model, co-immunoprecipitation, ubiquitination assays, RANKL expression analysis, osteoclast number quantification Nature communications High 28216630
2017 RNF11 directly competes with SMAD7 for binding to SMURF2 in a mutually exclusive, proline-rich domain-dependent manner; when RNF11 sequesters SMURF2 on endomembranes, it activates SMURF2 E3 ligase activity while reducing SMURF2 auto-ubiquitination, antagonizing the SMAD7-mediated downregulation of TGFβ signaling. In vitro reconstitution of SMURF2·RNF11 complex, in vitro binding competition assays, co-immunoprecipitation, in vivo ubiquitination assays, siRNA knockdown with TGFβ gene reporter assays The Journal of biological chemistry High 28292929
2018 Smurf2 directly binds, ubiquitinates, and promotes autophagic-lysosomal degradation (not solely proteasomal) of lamin A and progerin in a dose- and E3 ligase-dependent manner. Acute Smurf2 overexpression in progeria fibroblasts significantly reduces nuclear deformability. Co-immunoprecipitation, in vivo ubiquitination assays, autophagy/lysosome inhibitor experiments, Smurf2 overexpression/depletion, nuclear morphology quantification in progeria cells Aging cell Medium 29405587
2012 Smurf2 deficiency in mice impairs senescence of primary MEFs (reduced p16) and increases susceptibility to spontaneous B-cell lymphoma; premalignant spleens show defective senescence responses, genetically linking Smurf2-mediated senescence regulation to tumor suppression in vivo. Smurf2 knockout mouse generation, primary MEF senescence assays, tumor incidence monitoring, immunohistochemistry Cancer research High 22552287
2019 SMURF2 interacts with ChREBP and promotes its ubiquitination and proteasomal degradation; loss of SMURF2 increases ChREBP, enhances aerobic glycolysis, and promotes colorectal cancer cell proliferation. AKT acts as an upstream suppressor of SMURF2 to protect ChREBP from degradation. Co-immunoprecipitation, in vivo ubiquitination assay, siRNA/overexpression experiments, glycolysis/oxygen consumption measurements, in vivo xenograft The Journal of biological chemistry Medium 31409643
2019 SMURF2 interacts with SATB1 and promotes its ubiquitination and degradation; SMURF2 is itself negatively regulated by the deubiquitinase USP47, establishing a USP47-SMURF2-SATB1 axis controlling colon cancer cell proliferation. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, mouse xenograft model Cancer letters Medium 30742943
2019 TRAF4 acts as an E3 ubiquitin ligase that mediates K48-linked ubiquitination of Smurf2 at the K119 site, promoting Smurf2 proteasomal degradation, thereby increasing BMP/TGF-β signaling and osteogenic differentiation of mesenchymal stem cells. Co-immunoprecipitation, in vitro/in vivo ubiquitination assays, K119 site-directed mutagenesis, osteogenic differentiation assays, in vivo bone formation model Cell death and differentiation Medium 31076633
2016 Nedd8 targets Smurf2 for neddylation, which promotes Smurf2 degradation; Smurf2 itself exerts Nedd8 ligase activity, and Smurf1 neddylation activates its ubiquitin ligase activity. In vivo neddylation assays, co-immunoprecipitation, Western blot stability assays Biochemical and biophysical research communications Low 27086113
2019 PRMT5 sustains RNF168 expression; loss of PRMT5 (in MTAP-deficient glioblastoma) reduces RNF168, allowing SMURF2 to destabilize H2AX. RNF168 and SMURF2 act as stabilizer and destabilizer of H2AX respectively via dynamic interactions with H2AX, defining a PRMT5-RNF168-SMURF2 cascade controlling H2AX proteostasis. Co-immunoprecipitation, ubiquitination assays, genetic KD experiments, DNA damage response assays Cell reports Medium 31533041
2020 SMURF2 interacts with SIRT1 and mediates its ubiquitination and proteasomal degradation; depletion of SMURF2 leads to SIRT1 upregulation and promotes colorectal cancer tumor formation and growth in vitro and in vivo. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, in vivo tumor xenograft Oncogene Medium 32361710
2020 Dishevelled (DVL), a key Wnt pathway transducer, activates Smurf2 E3 ligase activity and is itself a substrate of Smurf2; DVL deficiency phenocopies Smurf2 absence, leading to increased R-Smad phosphorylation. Smurf2 also ubiquitinates Prickle1 (Wnt/PCP component). Both SMAD7 and DVL activate Smurf2 through a common mechanism. Co-immunoprecipitation, in vivo ubiquitination assays, DVL triple-knockout HEK293 cells, R-Smad phosphorylation assays Cells Medium 32392721
2020 Smurf2 negatively regulates BMP/Smad1/5 signaling by inducing ubiquitination of Smad1/5; Smurf2-deficient mice show enhanced BMP2-induced ectopic bone formation with greater bone mass and osteoblast numbers. Smurf2 knockout mouse, ectopic bone formation assay with rhBMP2, in vivo ubiquitination assay, primary bone marrow stromal cell differentiation assays Bone research Medium 33298874
2008 Smurf2 interacts with TRAF2 (identified by yeast two-hybrid), and TRAF2 overexpression triggers Smurf2 ubiquitination and formation of a TNF-R2/Smurf2 complex; Smurf2 in turn promotes TNF-R2 ubiquitination and relocalization to a detergent-insoluble fraction, which is associated with enhanced TNF-R2-induced JNK activation without affecting NF-κB. Yeast two-hybrid, co-immunoprecipitation, ubiquitination assays, detergent fractionation, JNK/NF-κB signaling assays Biochemical and biophysical research communications Low 18671942
2011 SMURF2 interacts with EGFR and promotes its ubiquitination (non-degradative/stabilizing), protecting EGFR from c-Cbl-mediated degradation. SMURF2 knockdown destabilizes EGFR, triggers autophagy, and reduces clonogenic survival of EGFR-expressing cancer cells. Co-immunoprecipitation, in vivo ubiquitination assays, siRNA knockdown, autophagic response assays, in vivo tumor model Neoplasia Medium 21750651 32669362
2020 SMURF2-UBCH5 E3-E2 complex mediates polyubiquitination of L858R/T790M EGFR at four specific lysine residues, stabilizing mutant EGFR by membrane retention and competing with acetylation-driven receptor internalization to lysosomes; SMURF2 knockdown increases lysosomal sorting of EGFR. In vitro and in vivo ubiquitination assays, mass spectrometry (ubiquitination site mapping), superresolution microscopy, acetylation-mimicking mutant (K→Q), siRNA knockdown The Journal of biological chemistry High 32669362
2022 SMURF2 phosphorylation at Thr249 activates its E3 ubiquitin ligase activity; inactivation of this phosphorylation site (T249A mutant) increases TGF-β receptor (TGFBR1) protein stability, augments glioma stem cell (GSC) stemness and tumorigenicity, phenocopying SMURF2 silencing. Phospho-specific mutant (T249A) overexpression, TGFBR1 stability assays, GSC sphere and tumor formation assays, TGFBR1 knockdown rescue experiments Communications biology Medium 35017630
2022 FMO2 binds CYP2J3 and disrupts CYP2J3 interaction with SMURF2 in the cytosol, leading to increased cytoplasm-to-nucleus translocation of SMURF2 and consequent inhibition of SMAD2/3 signaling and cardiac fibrosis; this antifibrotic mechanism is independent of FMO2 enzymatic activity. Co-immunoprecipitation, subcellular fractionation, CRISPR KO rats, gain-of-function lentivirus experiments, SMAD2/3 phosphorylation assays, cardiac fibrosis histology Circulation research Medium 35861735
2023 SMURF2 ubiquitinates and promotes degradation of GSTP1 at early stages of ferroptosis; GSTP1 functions as a GPX4- and FSP1-independent ferroptosis defense by catalyzing GSH conjugation of 4-HNE and detoxifying lipid hydroperoxides. Genetic or pharmacological modulation of the SMURF2/GSTP1 axis sensitizes tumors to ferroptosis-inducing drugs. Proteomics (dynamics during ferroptosis), co-immunoprecipitation, in vivo ubiquitination assay, GSTP1 catalytic activity assays, genetic overexpression/KD, in vitro and in vivo drug sensitivity assays Molecular cell High 38016474
2023 SMURF2 acts as a bona fide E3 ligase for RACK1, adding K6, K33, and K48 ubiquitin chains to RACK1, resulting in its polyubiquitination and degradation. PCAF-mediated acetylation of RACK1 at K130 inhibits SMURF2-mediated RACK1 ubiquitination, stabilizing RACK1 and promoting ovarian cancer progression. Co-immunoprecipitation, in vivo ubiquitination assay (linkage-specific), acetylation assay, PCAF overexpression, in vivo tumor model Cell death and differentiation Medium 37828084
2012 TGF-β induces SIK1 expression via Smad-dependent transcription; SIK1 forms complexes with the TGFβ type I receptor and Smurf2, and both SIK1 kinase activity and Smurf2 ubiquitin ligase activity are required for proper TGFβ type I receptor turnover. Knockdown of SIK1 and Smurf2 enhances physiological TGFβ-induced epithelial growth arrest. Co-immunoprecipitation, kinase and ubiquitination assays, siRNA knockdown, receptor turnover assays, promoter mapping The Journal of biological chemistry Medium 22378783
2004 RNF11 recruits AMSH to Smurf2 for ubiquitination and degradation by the 26S proteasome; RNF11 binds AMSH independently of its RING-finger domain and PY motif, and AMSH ubiquitination requires both RNF11 and Smurf2. Co-immunoprecipitation, yeast two-hybrid, in vivo ubiquitination assay Oncogene Low 14755250
2019 SMURF2 acts as an E3 ligase to mediate ubiquitination and degradation of RhoA; the oncoprotein AAMP stabilizes RhoA by binding to it and suppressing SMURF2-mediated RhoA ubiquitination and degradation, thereby promoting colorectal cancer cell migration and invasion. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, cell migration/invasion assays Molecular therapy oncolytics Low 34901393
2020 SMURF2 interacts with and promotes ubiquitination and degradation of PARP1; this interaction is enhanced under oxidative stress, and Smurf2-mediated PARP1 degradation reduces ROS and protects endothelial cells from apoptosis. Co-immunoprecipitation, in vivo ubiquitination assay, ROS/apoptosis assays in HUVECs Journal of cellular and molecular medicine Low 32167680
2017 Smurf2 interacts with PDE4B and facilitates its degradation, thereby activating the cAMP-PKA-CREB signaling pathway, which transcriptionally upregulates miR-132 to suppress CTGF expression and attenuate liver fibrosis. Co-immunoprecipitation, Smurf2 transgenic mouse model, miRNA array, western blot, CREB signaling assays Biochimica et biophysica acta. Molecular cell research Low 29100790
2019 SMURF2 interacts with CNKSR2 and promotes its stabilization (protective ubiquitination against proteasomal degradation); Smurf2 knockdown decreases CNKSR2 and reduces PI3K-PTEN-AKT-FoxO3a-driven proliferation of breast cancer cells. Co-immunoprecipitation, surface plasmon resonance, indirect immunofluorescence, ubiquitination assays, siRNA knockdown, proliferation assays BMC cancer Medium 29534682
2019 In normal cells and tissues, SMURF2 has a predominantly nuclear localization; in prostate and aggressive breast carcinomas, SMURF2 shows significantly increased cytoplasmic sequestration associated with disease progression. Biochemical studies showed SMURF2 is more stable in the cytoplasmic compartment, and 14-3-3 proteins are SMURF2 interactors that may affect its localization. Subcellular fractionation, immunohistochemistry of 666 tissue samples, co-immunoprecipitation (interactome), nuclear export inhibitor experiments Cancers Medium 31003445

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Molecular cell 1150 11163210
2001 Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase. Proceedings of the National Academy of Sciences of the United States of America 427 11158580
2000 Smurf2 is a ubiquitin E3 ligase mediating proteasome-dependent degradation of Smad2 in transforming growth factor-beta signaling. The Journal of biological chemistry 420 11016919
2001 TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation. Nature cell biology 269 11389444
2005 Tumor necrosis factor promotes Runx2 degradation through up-regulation of Smurf1 and Smurf2 in osteoblasts. The Journal of biological chemistry 265 16373342
2007 Autoinhibition of the HECT-type ubiquitin ligase Smurf2 through its C2 domain. Cell 233 17719543
2005 Regulation of Smurf2 ubiquitin ligase activity by anchoring the E2 to the HECT domain. Molecular cell 223 16061177
2012 A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20. Nature medicine 138 22231558
2011 Ablation of Smurf2 reveals an inhibition in TGF-β signalling through multiple mono-ubiquitination of Smad3. The EMBO journal 124 22045334
2008 Induction of an osteoarthritis-like phenotype and degradation of phosphorylated Smad3 by Smurf2 in transgenic mice. Arthritis and rheumatism 100 18821706
2023 SMURF2 predisposes cancer cell toward ferroptosis in GPX4-independent manners by promoting GSTP1 degradation. Molecular cell 98 38016474
2014 Smurf2 negatively modulates RIG-I-dependent antiviral response by targeting VISA/MAVS for ubiquitination and degradation. Journal of immunology (Baltimore, Md. : 1950) 93 24729608
2013 Smurf2-mediated degradation of EZH2 enhances neuron differentiation and improves functional recovery after ischaemic stroke. EMBO molecular medicine 93 23526793
2014 Akt enhances Runx2 protein stability by regulating Smurf2 function during osteoblast differentiation. The FEBS journal 90 24961731
2012 Effect of SMURF2 targeting on susceptibility to MEK inhibitors in melanoma. Journal of the National Cancer Institute 90 23250956
2014 KRAS protein stability is regulated through SMURF2: UBCH5 complex-mediated β-TrCP1 degradation. Neoplasia (New York, N.Y.) 87 24709419
2008 Smurf2 induces ubiquitin-dependent degradation of Smurf1 to prevent migration of breast cancer cells. The Journal of biological chemistry 83 18927080
2020 Ubiquitination-mediated degradation of SIRT1 by SMURF2 suppresses CRC cell proliferation and tumorigenesis. Oncogene 81 32361710
2012 CD109-mediated degradation of TGF-β receptors and inhibition of TGF-β responses involve regulation of SMAD7 and Smurf2 localization and function. Journal of cellular biochemistry 80 21898545
2003 The RING-H2 protein RNF11 is overexpressed in breast cancer and is a target of Smurf2 E3 ligase. British journal of cancer 78 14562029
2014 Fucoidan inhibition of lung cancer in vivo and in vitro : role of the Smurf2-dependent ubiquitin proteasome pathway in TGFβ receptor degradation. Oncotarget 77 25149540
2004 Smurf2 up-regulation activates telomere-dependent senescence. Genes & development 77 15574587
2010 The protein stability of Axin, a negative regulator of Wnt signaling, is regulated by Smad ubiquitination regulatory factor 2 (Smurf2). The Journal of biological chemistry 75 20858899
2019 Reversible regulation of SATB1 ubiquitination by USP47 and SMURF2 mediates colon cancer cell proliferation and tumor progression. Cancer letters 74 30742943
2007 Ubiquitination of the GTPase Rap1B by the ubiquitin ligase Smurf2 is required for the establishment of neuronal polarity. The EMBO journal 74 17318188
2017 SMURF2 regulates bone homeostasis by disrupting SMAD3 interaction with vitamin D receptor in osteoblasts. Nature communications 73 28216630
2013 Smurf2 suppresses B-cell proliferation and lymphomagenesis by mediating ubiquitination and degradation of YY1. Nature communications 70 24121673
2015 The ubiquitin ligase Smurf2 suppresses TGFβ-induced epithelial-mesenchymal transition in a sumoylation-regulated manner. Cell death and differentiation 64 26679521
2019 MiR-195 and miR-497 suppress tumorigenesis in lung cancer by inhibiting SMURF2-induced TGF-β receptor I ubiquitination. Molecular oncology 61 31581360
2014 Inhibition of Smurf2 translation by miR-322/503 modulates TGF-β/Smad2 signaling and intestinal epithelial homeostasis. Molecular biology of the cell 61 24554769
2019 TRAF4 positively regulates the osteogenic differentiation of mesenchymal stem cells by acting as an E3 ubiquitin ligase to degrade Smurf2. Cell death and differentiation 60 31076633
2015 miR-15b promotes epithelial-mesenchymal transition by inhibiting SMURF2 in pancreatic cancer. International journal of oncology 59 26166038
2004 An RNF11: Smurf2 complex mediates ubiquitination of the AMSH protein. Oncogene 57 14755250
2008 The HECT E3 ligase Smurf2 is required for Mad2-dependent spindle assembly checkpoint. The Journal of cell biology 56 18852296
2021 miR-19b enhances osteogenic differentiation of mesenchymal stem cells and promotes fracture healing through the WWP1/Smurf2-mediated KLF5/β-catenin signaling pathway. Experimental & molecular medicine 55 34035464
2009 Smurf2 induces degradation of GSK-3beta and upregulates beta-catenin in chondrocytes: a potential mechanism for Smurf2-induced degeneration of articular cartilage. Experimental cell research 55 19481076
2011 Smurf2-mediated ubiquitination and degradation of Id1 regulates p16 expression during senescence. Aging cell 54 21933340
2006 An expanded WW domain recognition motif revealed by the interaction between Smad7 and the E3 ubiquitin ligase Smurf2. The Journal of biological chemistry 49 16641086
2005 Transcriptional induction of Smurf2 ubiquitin ligase by TGF-beta. FEBS letters 49 15862290
2015 USP15 regulates SMURF2 kinetics through C-lobe mediated deubiquitination. Scientific reports 46 26435193
2011 Regulation of EGFR protein stability by the HECT-type ubiquitin ligase SMURF2. Neoplasia (New York, N.Y.) 46 21750651
2021 MiR-195 inhibits the ubiquitination and degradation of YY1 by Smurf2, and induces EMT and cell permeability of retinal pigment epithelial cells. Cell death & disease 44 34267179
2017 Smurf2, an E3 ubiquitin ligase, interacts with PDE4B and attenuates liver fibrosis through miR-132 mediated CTGF inhibition. Biochimica et biophysica acta. Molecular cell research 43 29100790
2018 USF2 inhibits the transcriptional activity of Smurf1 and Smurf2 to promote breast cancer tumorigenesis. Cellular signalling 42 30244169
2012 Smurf2 regulates the senescence response and suppresses tumorigenesis in mice. Cancer research 42 22552287
2019 TTC3 contributes to TGF-β1-induced epithelial-mesenchymal transition and myofibroblast differentiation, potentially through SMURF2 ubiquitylation and degradation. Cell death & disease 40 30696809
2020 A novel negative regulatory mechanism of Smurf2 in BMP/Smad signaling in bone. Bone research 39 33298874
2019 The ubiquitination ligase SMURF2 reduces aerobic glycolysis and colorectal cancer cell proliferation by promoting ChREBP ubiquitination and degradation. The Journal of biological chemistry 39 31409643
2014 Smurf2 regulates the degradation of YY1. Biochimica et biophysica acta 39 24803334
2018 Smurf2 regulates stability and the autophagic-lysosomal turnover of lamin A and its disease-associated form progerin. Aging cell 38 29405587
2014 Downregulation of Smurf2, a tumor-suppressive ubiquitin ligase, in triple-negative breast cancers: involvement of the RB-microRNA axis. BMC cancer 38 24485087
2014 Smurf2 E3 ubiquitin ligase modulates proliferation and invasiveness of breast cancer cells in a CNKSR2 dependent manner. Cell division 38 25191523
2019 A PRMT5-RNF168-SMURF2 Axis Controls H2AX Proteostasis. Cell reports 37 31533041
2009 c-Ski, Smurf2, and Arkadia as regulators of TGF-beta signaling: new targets for managing myofibroblast function and cardiac fibrosis. Canadian journal of physiology and pharmacology 37 19898560
2020 The Post-translational Modifications of Smurf2 in TGF-β Signaling. Frontiers in molecular biosciences 36 32733916
2017 The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness. Oncotarget 34 28423498
2014 Bortezomib prevents oncogenesis and bone metastasis of prostate cancer by inhibiting WWP1, Smurf1 and Smurf2. International journal of oncology 34 25051198
2021 TMAO Aggregates Neurological Damage Following Ischemic Stroke by Promoting Reactive Astrocytosis and Glial Scar Formation via the Smurf2/ALK5 Axis. Frontiers in cellular neuroscience 33 33815059
2021 Schisandrin B Attenuates Colitis-Associated Colorectal Cancer through SIRT1 Linked SMURF2 Signaling. The American journal of Chinese medicine 33 34632965
2023 Loss of SMURF2 expression enhances RACK1 stability and promotes ovarian cancer progression. Cell death and differentiation 32 37828084
2022 CBX3 Regulated By YBX1 Promotes Smoking-induced Pancreatic Cancer Progression via Inhibiting SMURF2 Expression. International journal of biological sciences 32 35637952
2022 Flavin Containing Monooxygenase 2 Prevents Cardiac Fibrosis via CYP2J3-SMURF2 Axis. Circulation research 32 35861735
2020 Long noncoding RNA SMUL suppresses SMURF2 production-mediated muscle atrophy via nonsense-mediated mRNA decay. Molecular therapy. Nucleic acids 32 33510940
2019 Inhibition of Smurf2 translation by miR-322/503 protects from ischemia-reperfusion injury by modulating EZH2/Akt/GSK3β signaling. American journal of physiology. Cell physiology 32 30649914
2016 Oncogenic Mutation of AIMP2/p38 Inhibits Its Tumor-Suppressive Interaction with Smurf2. Cancer research 30 27197155
2015 TRAF4-SMURF2-mediated DAZAP2 degradation is critical for IL-25 signaling and allergic airway inflammation. Journal of immunology (Baltimore, Md. : 1950) 30 25681341
2012 Transcriptional induction of salt-inducible kinase 1 by transforming growth factor β leads to negative regulation of type I receptor signaling in cooperation with the Smurf2 ubiquitin ligase. The Journal of biological chemistry 30 22378783
2007 The interaction of mPar3 with the ubiquitin ligase Smurf2 is required for the establishment of neuronal polarity. The Journal of biological chemistry 30 17906294
2018 MicroRNA-485 Modulates the TGF-β/ Smads Signaling Pathway in Chronic Asthmatic Mice by Targeting Smurf2. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 29 30463065
2008 Overexpression of Smurf2 stimulates endochondral ossification through upregulation of beta-catenin. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 29 18052755
2014 Efficient Conversion of Spermatogonial Stem Cells to Phenotypic and Functional Dopaminergic Neurons via the PI3K/Akt and P21/Smurf2/Nolz1 Pathway. Molecular neurobiology 27 25373443
2017 RNF11 sequestration of the E3 ligase SMURF2 on membranes antagonizes SMAD7 down-regulation of transforming growth factor β signaling. The Journal of biological chemistry 26 28292929
2016 Ovatodiolide Inhibits Breast Cancer Stem/Progenitor Cells through SMURF2-Mediated Downregulation of Hsp27. Toxins 25 27136586
2020 MiR-411-3p alleviates Silica-induced pulmonary fibrosis by regulating Smurf2/TGF-β signaling. Experimental cell research 24 32004504
2017 Smurf2-Mediated Stabilization of DNA Topoisomerase IIα Controls Genomic Integrity. Cancer research 24 28611047
2022 Inhibition of ChREBP ubiquitination via the ROS/Akt-dependent downregulation of Smurf2 contributes to lysophosphatidic acid-induced fibrosis in renal mesangial cells. Journal of biomedical science 22 35538534
2020 The E3 ubiquitin ligase Smurf2 regulates PARP1 stability to alleviate oxidative stress-induced injury in human umbilical vein endothelial cells. Journal of cellular and molecular medicine 22 32167680
2020 MiR-497-5p Regulates Osteo/Odontogenic Differentiation of Stem Cells From Apical Papilla via the Smad Signaling Pathway by Targeting Smurf2. Frontiers in genetics 22 33193708
2015 AKT regulation of mesothelial-to-mesenchymal transition in peritoneal dialysis is modulated by Smurf2 and deubiquitinating enzyme USP4. BMC cell biology 22 25885904
2016 Nedd8 targets ubiquitin ligase Smurf2 for neddylation and promote its degradation. Biochemical and biophysical research communications 21 27086113
2022 SMURF2 phosphorylation at Thr249 modifies glioma stemness and tumorigenicity by regulating TGF-β receptor stability. Communications biology 20 35017630
2019 Altered Expression and Localization of Tumor Suppressive E3 Ubiquitin Ligase SMURF2 in Human Prostate and Breast Cancer. Cancers 20 31003445
2016 Skeletal Characterization of Smurf2-Deficient Mice and In Vitro Analysis of Smurf2-Deficient Chondrocytes. PloS one 20 26815610
2015 The downregulation of SnoN expression in human renal proximal tubule epithelial cells under high-glucose conditions is mediated by an increase in Smurf2 expression through TGF-β1 signaling. International journal of molecular medicine 20 26743567
2011 RLIM interacts with Smurf2 and promotes TGF-β induced U2OS cell migration. Biochemical and biophysical research communications 20 21945933
2010 The WW-HECT protein Smurf2 interacts with the Docking Protein NEDD9/HEF1 for Aurora A activation. Cell division 20 20825672
2009 Smurf2 participates in human trophoblast cell invasion by inhibiting TGF-beta type I receptor. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 20 19255252
2021 Smurf2 exerts neuroprotective effects on cerebral ischemic injury. The Journal of biological chemistry 19 33722608
2021 AAMP promotes colorectal cancermetastasis by suppressing SMURF2-mediatedubiquitination and degradation of RhoA. Molecular therapy oncolytics 19 34901393
2018 Regulation of CNKSR2 protein stability by the HECT E3 ubiquitin ligase Smurf2, and its role in breast cancer progression. BMC cancer 19 29534682
2008 Suppression of human tumor cell proliferation by Smurf2-induced senescence. Journal of cellular physiology 19 18181147
2008 Smurf2 is a TRAF2 binding protein that triggers TNF-R2 ubiquitination and TNF-R2-induced JNK activation. Biochemical and biophysical research communications 19 18671942
2006 Abnormal expression of Smurf2 during the process of rat liver fibrosis. Chinese journal of digestive diseases 19 17054587
2020 Activity of Smurf2 Ubiquitin Ligase Is Regulated by the Wnt Pathway Protein Dishevelled. Cells 18 32392721
2022 Smurf2 inhibition enhances chemotherapy and radiation sensitivity in non-small-cell lung cancer. Scientific reports 17 35710591
2021 E3 ubiquitin ligase SMURF2 prevents colorectal cancer by reducing the stability of the YY1 protein and inhibiting the SENP1/c-myc axis. Gene therapy 17 34545207
2020 Ubiquitin ligase SMURF2 enhances epidermal growth factor receptor stability and tyrosine-kinase inhibitor resistance. The Journal of biological chemistry 17 32669362
2023 The miR-15b-Smurf2-HSP27 axis promotes pulmonary fibrosis. Journal of biomedical science 16 36611161
2020 SMURF2 prevents detrimental changes to chromatin, protecting human dermal fibroblasts from chromosomal instability and tumorigenesis. Oncogene 16 32103168
2016 Downregulation of Smurf2 ubiquitin ligase in pancreatic cancer cells reversed TGF-β-induced tumor formation. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 27730540

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