Affinage

SMURF1

E3 ubiquitin-protein ligase SMURF1 · UniProt Q9HCE7

Length
757 aa
Mass
86.1 kDa
Annotated
2026-04-28
100 papers in source corpus 50 papers cited in narrative 50 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SMURF1 is a HECT-domain E3 ubiquitin ligase that serves as a central negative regulator of BMP/TGF-β signaling, bone homeostasis, cell polarity, migration, autophagy, and innate immunity through ubiquitin-dependent degradation or non-degradative modification of a broad substrate repertoire. It ubiquitinates BMP receptors and Smad1/5 (via Smad6/7 adaptors), the osteoblast transcription factor Runx2, the JNK pathway kinase MEKK2, and the Rho GTPases RhoA and RhoB, thereby controlling osteoblast differentiation, neuronal polarity, and tumor cell motility (PMID:12857866, PMID:12738770, PMID:15820682, PMID:16540523, PMID:25249323). Beyond canonical K48-linked degradation, SMURF1 assembles K63-, K29-, and K33-linked polyubiquitin chains on substrates including PPARγ, Axin, TRAF4, and UVRAG to regulate transcription, Wnt signaling, tight-junction dynamics, and autophagosome maturation, and also catalyzes neddylation of PDK1 and RRP9 to activate PI3K-Akt signaling and ribosome biogenesis (PMID:30566427, PMID:24700460, PMID:23760265, PMID:30686098, PMID:39039255, PMID:34662580). Its activity is regulated by autoinhibitory homodimerization (relieved by Cdh1), neddylation at C426, phosphorylation by PKA (T306), ERK (T223), AMPK (S148), and Chk1, the co-activator CKIP-1, and turnover mediated by SCF(FBXL15), Smurf2, and the deubiquitinase USP9X (PMID:22152476, PMID:24821572, PMID:21262463, PMID:35654587, PMID:27052174, PMID:18641638, PMID:21572392, PMID:23184937). The C2 domain directs plasma-membrane targeting and substrate selectivity (favoring RhoA over Smad/Runx2), WW domains recognize PY-motif substrates, and CRM1-dependent nuclear export of the Smurf1–Smad7 complex enables cytoplasmic receptor degradation (PMID:21402695, PMID:12519765).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2003 High

    Establishing SMURF1 as a multi-level negative regulator of BMP signaling — it was unclear how one E3 ligase could attenuate the pathway at both receptor and Smad levels; demonstration that Smurf1, via inhibitory Smads, ubiquitinates and degrades both BMP type I receptors and R-Smads (Smad1/5) revealed cooperative pathway suppression, while CRM1-dependent nuclear export of the Smurf1–Smad7 complex explained how a nuclear-assembled complex reaches cytoplasmic receptors.

    Evidence Co-IP, ubiquitination assays, Xenopus axis duplication, BMP reporters, NES mutagenesis and leptomycin B treatment in mammalian cells

    PMID:12519765 PMID:12857866

    Open questions at the time
    • Stoichiometry of Smurf1–I-Smad complexes on receptors not determined
    • Relative contribution of receptor versus Smad degradation to BMP signal termination unknown
  2. 2003 High

    Identifying Runx2 as a direct SMURF1 substrate connected the ligase to osteoblast differentiation and bone formation — previously, SMURF1 function was understood only through BMP receptor/Smad degradation.

    Evidence Co-IP, ubiquitination assay, proteasome inhibitors, transgenic mice overexpressing Smurf1 in osteoblasts showing reduced bone formation

    PMID:12738770

    Open questions at the time
    • Whether Smurf1 targets Runx2 through a PY-motif or alternative docking site was not fully mapped
  3. 2005 High

    Discovery that Smurf1 ubiquitinates MEKK2 and that Smurf1-knockout mice accumulate bone mass established a Smad-independent pathway (JNK signaling) through which SMURF1 controls osteoblast activity.

    Evidence Co-IP, ubiquitination assays, Smurf1-KO mouse with age-dependent bone mass increase, epistasis with JNK pathway

    PMID:15820682

    Open questions at the time
    • How Smurf1 recognizes MEKK2 (binding motif/domain) was not mapped
    • Relative in vivo contribution of MEKK2 vs. Runx2 degradation to the KO bone phenotype unresolved
  4. 2005 High

    Demonstrating that SMURF1 ubiquitinates RhoA and promotes its proteasomal degradation opened a new functional axis — regulation of cytoskeletal dynamics, cell polarity, and neuronal morphogenesis — beyond TGF-β/BMP signaling.

    Evidence Co-IP, ubiquitination assays in Neuro2a cells, proteasome inhibitor, neurite outgrowth measurement; confirmed by Smurf1-KO and siRNA in multiple subsequent studies

    PMID:15710384 PMID:16540523

    Open questions at the time
    • Structural basis for Smurf1 selectivity toward GTP-loaded RhoA was not resolved
  5. 2006 High

    Linking SMURF1-mediated RhoA degradation to tumor cell motility mode revealed that Smurf1 activity determines mesenchymal versus amoeboid migration, with Smurf1 loss paradoxically increasing invasiveness in 3D.

    Evidence Smurf1 siRNA, ROCK/MLC2 phosphorylation assays, 2D/3D invasion assays, in vivo migration

    PMID:17190792

    Open questions at the time
    • Whether Smurf1 regulation of migration is solely through RhoA or involves additional substrates was not resolved
  6. 2008 High

    Identification of CKIP-1 as a Smurf1-specific co-activator, binding the inter-WW linker and enhancing substrate affinity, provided the first mechanism for positive regulation of SMURF1 catalytic output — CKIP-1-KO mice phenocopied bone mass increases.

    Evidence Co-IP, domain mapping, in vitro ubiquitination, CKIP-1-KO mouse phenotyping

    PMID:18641638

    Open questions at the time
    • Structural basis of CKIP-1–Smurf1 interaction not determined
    • Whether CKIP-1 regulates all or only bone-related Smurf1 substrates unknown
  7. 2008 High

    Discovery that Smurf2 ubiquitinates Smurf1 (but not vice versa) established an asymmetric cross-regulation between the two paralogous ligases with consequences for migration and metastasis.

    Evidence Co-IP, ubiquitination assay, Smurf2 siRNA elevating Smurf1 protein, in vivo bone metastasis model

    PMID:18927080

    Open questions at the time
    • Molecular basis for the asymmetry (why Smurf1 cannot ubiquitinate Smurf2) was not explained
  8. 2009 High

    Showing Smurf1 ubiquitinates talin head (regulated by Cdk5 phosphorylation) extended the substrate repertoire to integrin-based adhesion complexes, mechanistically linking Smurf1 to focal adhesion turnover.

    Evidence Co-IP, in vitro ubiquitination, S425A mutagenesis, focal adhesion imaging, cell migration assays

    PMID:19363486

    Open questions at the time
    • Whether calpain-generated talin head is the sole adhesion substrate or Kindlin-2 (later discovered) also contributes was not known
  9. 2011 High

    Multiple regulatory layers were resolved simultaneously: Cdh1 activates Smurf1 by disrupting an autoinhibitory homodimer (APC/C-independent); PKA phosphorylation at T306 switches substrate preference from Par6 to RhoA enabling axon specification; the C2 domain crystal structure revealed membrane-targeting lysines (K28/K85) that confer RhoA-over-Smad selectivity; and SCF(FBXL15) was identified as the first dedicated Smurf1-degrading ubiquitin ligase.

    Evidence Crystal structure, mutagenesis, in vitro ubiquitination with differential substrates, in utero electroporation, zebrafish morpholino, KD epistasis in osteoblasts

    PMID:21262463 PMID:21402695 PMID:21572392 PMID:22152476

    Open questions at the time
    • Whether homodimer disruption and C2-domain substrate selectivity operate independently or coordinately was unclear
    • FBXL15 regulation of Smurf1 in non-bone tissues not tested
  10. 2012 High

    SMURF1's role expanded to innate immunity: Ndfip1 enhances Smurf1-mediated MAVS ubiquitination and degradation, suppressing RIG-I-dependent interferon signaling. Separately, USP9X was identified as a deubiquitinase that stabilizes Smurf1 by counteracting its auto-ubiquitination.

    Evidence Co-IP, ubiquitination assays, Ndfip1 KD/OE with IFN-β reporter, MS interactome for USP9X, domain mapping, cell migration

    PMID:23087404 PMID:23184937

    Open questions at the time
    • Whether USP9X and Ndfip1 act on the same Smurf1 pool was not addressed
    • In vivo immune phenotype of Smurf1 deficiency regarding viral infection not tested in these studies
  11. 2014 High

    Neddylation was established as a novel activation mechanism: Smurf1 forms a thioester with Nedd8 at active-site C426 and auto-neddylates, dramatically enhancing ubiquitin E2 recruitment. Concurrently, Chk1 phosphorylation was shown to promote Smurf1 self-degradation after DNA damage, enabling RhoB-mediated apoptosis. K29-linked ubiquitination of Axin via the C2 domain linked Smurf1 to Wnt signaling regulation.

    Evidence In vitro neddylation, C426 mutagenesis, thioester trapping, Chk1 kinase assay, UV/MMS treatment, Axin domain mutagenesis and cell-cycle synchronization

    PMID:24700460 PMID:24821572 PMID:25249323

    Open questions at the time
    • Which specific ubiquitin E2s are recruited by neddylated Smurf1 was not determined
    • Physiological contexts where neddylation versus phosphorylation dominates Smurf1 regulation are unclear
  12. 2016 High

    Non-degradative ubiquitin chain diversity was demonstrated: K63-linked chains on PPARγ suppress its transcriptional activity (Smurf1-KO mice develop hepatic steatosis), AMPK phosphorylation at S148 is essential for in vivo Smurf1 function (knock-in mice phenocopy KO), and Smurf1 promotes selective autophagy of M. tuberculosis via K48-linked ubiquitination and C2-domain phospholipid binding.

    Evidence Smurf1-KO and S148A knock-in mice, ubiquitin linkage assays, PPARγ reporter, macrophage infection model, domain mutants

    PMID:27052174 PMID:28017659 PMID:30566427

    Open questions at the time
    • How AMPK-S148 phosphorylation mechanistically alters Smurf1 activity/conformation unknown
    • Whether PPARγ K63-ubiquitination affects its DNA binding, cofactor recruitment, or stability selectively was not resolved
  13. 2017 High

    Identification of Kindlin-2 as a Smurf1 substrate (but not Talin) linked Smurf1 to integrin inside-out activation control, complementing earlier talin-head findings and revealing substrate selectivity within adhesion signaling.

    Evidence Co-IP, ubiquitination assay, Smurf1-KO MEFs showing elevated Kindlin-2 and β1-integrin activation

    PMID:28404804

    Open questions at the time
    • How Smurf1 distinguishes Kindlin-2 from other FERM-domain proteins is unknown
    • In vivo adhesion/migration consequences in Smurf1-KO mice not fully explored
  14. 2019 High

    K29/K33-linked ubiquitination of UVRAG by SMURF1 promotes autophagosome maturation by disrupting UVRAG–Rubicon interaction, extending the non-degradative chain-type repertoire and establishing SMURF1 as a positive regulator of autophagy flux.

    Evidence In vitro ubiquitination, K517R/K559R mutagenesis, autophagy flux assays, in vivo tumor model, ZRANB1 DUB antagonism

    PMID:30686098

    Open questions at the time
    • Signal that triggers SMURF1-dependent UVRAG ubiquitination is unknown
    • Relationship between UVRAG and Mtb autophagy substrates of Smurf1 not tested
  15. 2021 High

    SMURF1 was shown to function as a neddylation E3 ligase for RRP9, with neddylation at K221 required for pre-rRNA processing and ribosome biogenesis — establishing a catalytic activity distinct from ubiquitination with direct relevance to cell proliferation.

    Evidence In vitro and in vivo neddylation assays, K221R mutagenesis, pre-rRNA processing analysis, tumor cell proliferation/migration assays

    PMID:34662580

    Open questions at the time
    • Scope of Smurf1 neddylation substrates beyond RRP9 and PDK1 unknown
    • Whether neddylation and ubiquitination activities are regulated independently is unresolved
  16. 2022 High

    ERK-mediated phosphorylation at T223 was shown to be required for Smurf1-dependent RhoA degradation during TGF-β-induced EMT, providing a direct signaling input from MAPK to the Smurf1–RhoA axis with consequences for metastasis.

    Evidence T223A mutagenesis, ubiquitination assay, EMT marker analysis, in vivo breast cancer lung metastasis model

    PMID:35654587

    Open questions at the time
    • Whether T223 and T306 phosphorylation can co-occur or are mutually exclusive is unknown
    • How ERK activation is spatially coordinated with Smurf1 membrane localization is unresolved
  17. 2024 High

    Discovery that SMURF1-catalyzed PDK1 neddylation recruits SETDB1 to form a cytoplasmic cCOMPASS complex that directs Akt membrane attachment and T308 phosphorylation revealed a non-ubiquitin, scaffold-level function of SMURF1 in PI3K-Akt oncogenic signaling.

    Evidence Co-IP, in vitro neddylation, Smurf1-KO mouse, PROTAC degrader (SMART-1), Akt phosphorylation and membrane localization in KRAS-mutant CRC

    PMID:39039255

    Open questions at the time
    • Whether the cCOMPASS complex operates in non-KRAS-mutant contexts is untested
    • Structural basis of PDK1 poly-Nedd8 chain recognition by SETDB1 is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include: how SMURF1's ubiquitination and neddylation activities are partitioned among its >20 substrates in different cell types; the structural basis for the autoinhibitory homodimer and its relief; whether SMURF1 plays causal roles in human Mendelian disease; and the therapeutic window for targeting SMURF1 in cancer given its dual tumor-suppressive (RhoA, PPARγ) and oncogenic (PTEN, Akt) functions.
  • No full-length Smurf1 structure (homodimer or monomer) has been solved
  • Comprehensive substrate profiling across tissues has not been performed
  • No human genetic disorder has been directly linked to SMURF1 mutations

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 18 GO:0016874 ligase activity 3 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1 GO:0005829 cytosol 1 GO:0005929 cilium 1
Pathway
R-HSA-392499 Metabolism of proteins 9 R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 3 R-HSA-9612973 Autophagy 3 R-HSA-1500931 Cell-Cell communication 2 R-HSA-1643685 Disease 2 R-HSA-1430728 Metabolism 1 R-HSA-5357801 Programmed Cell Death 1
Partners
CDH1CKIP1FBXL15NDFIP1RHOASMAD7SMURF2USP9X
Complex memberships
Smurf1 autoinhibitory homodimerSmurf1–Smad7 complexcCOMPASS (PDK1–Smurf1–SETDB1)

Evidence

Reading pass · 50 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Smurf1 physically interacts with MEKK2 and promotes its ubiquitination and proteasomal degradation, thereby suppressing JNK signaling and osteoblast activity independently of canonical Smad-mediated BMP signaling. Smurf1-deficient mice show age-dependent bone mass increase due to MEKK2 accumulation and JNK activation. Co-immunoprecipitation, ubiquitination assay, Smurf1-knockout mouse phenotyping, in vivo epistasis Cell High 15820682
2003 Smurf1 binds BMP type I receptors via inhibitory Smads (Smad6/7) and induces their ubiquitination and degradation; Smurf1 also associates with Smad1/5 indirectly through I-Smads to promote their ubiquitination and degradation, providing multiple cooperative mechanisms for BMP signal suppression. Co-immunoprecipitation, ubiquitination assay, Xenopus secondary axis assay, BMP-reporter assay in mammalian cells Molecular biology of the cell High 12857866
2003 Smurf1 directly interacts with the osteoblast transcription factor Runx2/Cbfa1 and mediates its ubiquitination and proteasomal degradation, reducing osteoblast differentiation. Transgenic mice overexpressing Smurf1 in osteoblasts show reduced bone formation. Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor experiments, transgenic mouse model The Journal of biological chemistry High 12738770
2014 Smurf1 is activated by neddylation: it physically interacts with Nedd8 and Ubc12, forms a Nedd8-thioester intermediate at active-site C426 in the HECT N-lobe, and catalyzes its own neddylation on multiple lysines. Neddylation of Smurf1 potently enhances ubiquitin E2 recruitment and augments its E3 ligase activity. Co-immunoprecipitation, in vitro neddylation assay, active-site mutagenesis (C426), thioester trapping, ubiquitin E2 recruitment assay Nature communications High 24821572
2016 Smurf1 facilitates selective autophagy of Mycobacterium tuberculosis in macrophages using both its ubiquitin-ligase activity and C2 phospholipid-binding domain, promoting K48-linked (not K63-linked) ubiquitination of Mtb-associated structures and recruitment of NBR1, LC3, and LAMP1. Smurf1-/- macrophages show impaired bacterial clearance. Smurf1-/- macrophage loss-of-function, domain mutant analysis, ubiquitin-linkage assay, immunofluorescence, in vivo infection model Cell host & microbe High 28017659
2009 Talin head (produced by calpain cleavage) binds Smurf1 more tightly than full-length talin and is ubiquitylated and degraded by Smurf1. Cdk5 phosphorylates talin head at Ser425, inhibiting its binding to Smurf1 and preventing its ubiquitylation, thereby stabilizing focal adhesions and maintaining cell migration. Co-immunoprecipitation, in vitro ubiquitylation assay, phosphorylation assay, mutagenesis (S425A), focal adhesion imaging, cell migration assay Nature cell biology High 19363486
2008 CKIP-1 interacts specifically with the linker region between WW domains of Smurf1 (not Smurf2), augmenting Smurf1's affinity for substrates and increasing its E3 ligase activity. CKIP-1-deficient mice show age-dependent bone mass increase due to reduced Smurf1 activity. Co-immunoprecipitation, domain mapping, in vitro ubiquitylation assay, CKIP-1 knockout mouse phenotyping Nature cell biology High 18641638
2011 PKA-dependent phosphorylation of Smurf1 at Thr306 switches its substrate preference: phosphorylated Smurf1 has reduced affinity for Par6 (sparing it from degradation) and increased degradation of RhoA, promoting axon formation in hippocampal and cortical neurons in vivo. Phosphorylation assay, site-directed mutagenesis (T306), substrate affinity measurements, in utero electroporation, hippocampal neuron culture Neuron High 21262463
2006 Smurf1-dependent RhoA ubiquitination and degradation at the cell periphery downregulates ROCK activity and myosin light chain 2 phosphorylation, enabling lamellipodia formation and tumor cell motility in 2D; inhibition of Smurf1 in 3D or in vivo induces a mesenchymal-to-amoeboid transition with increased invasiveness. Smurf1 siRNA knockdown, ROCK activity assay, MLC2 phosphorylation detection, 2D/3D invasion assays, in vivo tumor cell migration The Journal of cell biology High 17190792
2012 Ndfip1 enhances Smurf1 self-ubiquitination and its interaction with MAVS, promoting MAVS ubiquitination and proteasomal degradation, thereby suppressing RIG-I-dependent antiviral interferon signaling. Co-immunoprecipitation, ubiquitination assay, Ndfip1 knockdown/overexpression, IFN-β reporter assay, IRF-3 phosphorylation measurement Journal of immunology High 23087404
2019 SMURF1 ubiquitinates UVRAG at K517 and K559 with K29/K33-linked polyubiquitin chains, decreasing the UVRAG-RUBCN interaction and promoting autophagosome maturation. The deubiquitinase ZRANB1 removes these chains, restoring RUBCN binding and inhibiting autophagy flux. Co-immunoprecipitation, in vitro ubiquitination assay, mutagenesis (K517R/K559R), autophagy flux assay, in vivo tumor model Autophagy High 30686098
2012 USP9X (FAM) deubiquitinase interacts with Smurf1 via the second WW domain of Smurf1 and the C-terminus of USP9X, antagonizing Smurf1 auto-ubiquitination and proteasomal self-degradation, thereby stabilizing Smurf1 and supporting cell migration in breast cancer cells. Quantitative mass spectrometry interactome, Co-immunoprecipitation, domain mapping, deubiquitination assay, USP9X siRNA knockdown, cell migration assay The Journal of biological chemistry High 23184937
2011 Cdh1 promotes Smurf1 E3 ligase activity by disrupting an autoinhibitory Smurf1 homodimer in an APC/C-independent manner. Depletion of Cdh1 reduces Smurf1 activity, leading to MEKK2 accumulation and osteoblast differentiation. Co-immunoprecipitation, in vitro ubiquitination assay, Cdh1 knockdown in osteoblasts, epistasis with MEKK2 pathway Molecular cell High 22152476
2011 The Smurf1 C2 domain is not involved in autoinhibition (unlike Smurf2) but instead functions in substrate selection and plasma membrane localization via two key lysine residues (K28 and K85). The C2 domain confers preferential activity toward RhoA over Smad5 and Runx2 and is required for cell migration regulation. Crystal structure of C2 domain, mutagenesis (K28A/K85A), membrane fractionation, in vitro ubiquitination assay with different substrates, cell migration assay The Journal of biological chemistry High 21402695
2011 SCF(FBXL15) ubiquitin ligase complex targets Smurf1 for ubiquitination and proteasomal degradation by recognizing the N-lobe of the Smurf1 HECT domain and ubiquitinating K355/K357 in the WW-HECT linker, thereby positively regulating BMP signaling. Co-immunoprecipitation, in vitro ubiquitination assay, mutagenesis (K355/K357), zebrafish morpholino knockdown, siRNA injection in rat bone The EMBO journal High 21572392
2014 ATR/Chk1-dependent DNA damage response leads to Chk1-mediated phosphorylation of Smurf1, enhancing Smurf1 self-degradation. This causes RhoB accumulation, which promotes apoptosis. In basal state, Smurf1 targets RhoB for ubiquitination and degradation. Phosphorylation assay, ubiquitination assay, Chk1 kinase assay, Smurf1 overexpression/knockdown, UV/MMS DNA damage treatments, apoptosis assay Nature communications High 25249323
2010 Smurf1/2 promotes p53 degradation indirectly by stabilizing MDM2: Smurf1/2 interacts with both MDM2 and MDMX, enhancing MDM2-MDMX heterodimerization and thereby stabilizing MDM2 E3 ligase activity. This effect is independent of Smurf1's own E3 ligase activity. Co-immunoprecipitation, ubiquitination assay, MDM2-MDMX heterodimerization assay, apoptosis assay The Journal of biological chemistry Medium 20484049
2003 CRM1-dependent nuclear export of Smurf1, mediated by a functional NES in the C-terminal region of Smurf1, is required for nuclear export of the Smurf1-Smad7 complex to the cytoplasm where Smurf1-Smad7 can associate with and degrade TGF-β type I receptor. Leptomycin B treatment, GFP-NES fusion protein localization, CRM1 co-immunoprecipitation, NES mutagenesis, TGF-β reporter assay The Journal of biological chemistry High 12519765
2005 Tumor necrosis factor upregulates Smurf1 and Smurf2 expression in osteoblasts, leading to increased proteasomal degradation of Runx2; Smurf1 siRNA blocks TNF-induced Runx2 degradation and rescues BMP signaling reporter activity. siRNA knockdown, proteasome inhibitor (MG132), Western blot, BMP reporter assay, in vivo TNF transgenic and injection mouse models The Journal of biological chemistry High 16373342
2006 Smurf1 is a rate-limiting and specific factor for ubiquitin-mediated proteasomal degradation of GTP-activated (constitutively active) RhoA. Smurf1-deficient cells and Smurf1-knockdown cells fail to ubiquitylate CNF1-activated RhoA, and ectopic Smurf1 in deficient cells restores RhoA ubiquitylation. Smurf1-/- cells, siRNA knockdown, CNF1 toxin-activated RhoA ubiquitylation assay, ectopic expression rescue Molecular biology of the cell High 16540523
2010 Smurf1 interacts with and ubiquitinates JunB, targeting it for proteasomal degradation via the JunB PY motif. Loss of Smurf1 in mesenchymal stem cells causes JunB accumulation, increased cyclin D1 expression, enhanced proliferation, and elevated osteoblast differentiation. Co-immunoprecipitation, ubiquitination assay, PY-motif mutagenesis, Smurf1-/- MSC analysis, JunB knockdown rescue experiment Journal of bone and mineral research High 20200942
2008 Smurf2 interacts with Smurf1 and induces its ubiquitination and degradation (but not vice versa). Knockdown of Smurf2 in breast cancer cells elevates Smurf1 protein levels and enhances cell migration in vitro and bone metastasis in vivo. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, cell migration assay, in vivo bone metastasis model The Journal of biological chemistry High 18927080
2006 FKBP12 acts as an adaptor for the Smad7-Smurf1 complex on the activin type I receptor (ALK4), and FK506 (which displaces FKBP12) decreases Smad7-Smurf1 interaction and inhibits receptor ubiquitination by Smurf1. Co-immunoprecipitation, FK506 treatment, ubiquitination assay of ALK4 Journal of molecular endocrinology Medium 16720724
2011 Smurf1 interacts with WFS1 at the endoplasmic reticulum and promotes WFS1 ubiquitination and proteasomal degradation via a C-terminal luminal degron (residues 667-700). ER stress induces Smurf1 degradation and WFS1 upregulation in a reciprocal regulatory relationship. Co-immunoprecipitation, ubiquitination assay, domain deletion mutagenesis, RNAi knockdown, ER stress induction The Journal of biological chemistry Medium 21454619
2009 Smurf1 ubiquitinates all six TRAF family members, with TRAF4 validated via its PY motifs interacting with the second WW domain of Smurf1. Smurf1-mediated TRAF degradation suppresses NF-κB signaling. Yeast two-hybrid, Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor, NF-κB reporter assay Molecular and cellular biochemistry Medium 19937093
2013 Smurf1 induces non-degradative ubiquitination of TRAF4 at K190, which is required for proper TRAF4 localization to tight junctions and for TRAF4-dependent Rac1 activation and cell migration. K190R mutation of TRAF4 abolishes Smurf1-dependent migration. Co-immunoprecipitation, site-specific mutagenesis (K190R), ubiquitination assay, Rac1 activation assay, cell migration assay, tight junction localization imaging The Journal of biological chemistry High 23760265
2017 Smurf1 interacts with and ubiquitinates Kindlin-2 for proteasomal degradation, selectively degrading Kindlin-2 but not Talin, thereby reducing integrin activation. Smurf1-KO mouse embryonic fibroblasts show enhanced β1 integrin activation correlating with elevated Kindlin-2 levels. Co-immunoprecipitation, ubiquitination assay, Smurf1-KO MEFs, integrin activation assay (αIIbβ3, β1), Western blot of colon cancer tissues The Journal of cell biology High 28408404
2005 Smurf1 ubiquitinates RhoA and promotes its proteasomal degradation in neurons, leading to reduced RhoA protein levels during cAMP-induced (but not retinoic acid-induced) neurite outgrowth in Neuro2a cells. Co-immunoprecipitation, ubiquitination assay, proteasome inhibitor (MG132), Smurf1 overexpression, neurite outgrowth assay FEBS letters Medium 15710384
2010 REGγ proteasome activator interacts with Smurf1 and mediates its ubiquitin-independent degradation. REGγ overexpression promotes Smurf1 degradation while REGγ depletion stabilizes Smurf1, subsequently affecting Smad5 levels. Co-immunoprecipitation, overexpression/knockdown of REGγ, protein stability assay FEBS letters Medium 20580715
2008 Smurf1 targets hPEM-2 (a GEF for Cdc42) for proteasomal degradation through a non-canonical interaction: hPEM-2 PH domain (residues 318-343) binds the Smurf1 C2 domain (not WW domains) in a Ca2+-independent manner. GST pulldown, pulse-chase labeling, proteasome inhibitor (MG132) ubiquitination assay, domain mapping Biological chemistry Medium 18208356
2011 Smurf1 interacts with KLF2 and promotes its poly-ubiquitination and proteasomal degradation specifically in lung cancer H1299 cells, requiring Smurf1 catalytic activity, leading to repression of KLF2 target genes (CD62L, Wee1). Co-immunoprecipitation, ubiquitination assay, catalytic mutant of Smurf1, target gene expression analysis Biochemical and biophysical research communications Medium 21382345
2010 Smurf1 interacts with ING2 via the Smurf1 HECT domain (not WW domains), targeting ING2 for poly-ubiquitination and proteasomal degradation in a reaction requiring the C-terminal PHD domain of ING2. Co-immunoprecipitation, ubiquitination assay, domain mapping FEBS letters Medium 20621832
2016 Smurf1 promotes non-proteolytic K63-linked ubiquitination of PPARγ, suppressing its transcriptional activity without causing degradation. Smurf1-deficient mice spontaneously develop hepatic steatosis with elevated PPARγ and lipid synthesis gene expression. Smurf1-/- mouse model, ubiquitination linkage assay (K63 chains), PPARγ transcriptional activity reporter, high-fat diet model, PPARγ antagonist rescue (GW9662) PLoS biology High 30566427
2014 Smurf1 mediates K29-linked poly-ubiquitination of Axin, requiring its C2 domain (not WW domains) for the interaction. Plasma membrane localization of Smurf1 via its C2 domain is required for Axin ubiquitination, and this interaction is attenuated in G2/M phase of the cell cycle. Co-immunoprecipitation, ubiquitination assay, domain mutagenesis, cell-cycle synchronization, localization imaging The Journal of biological chemistry Medium 24700460
2016 SMURF1 associates with the N-terminal domain of ERα via its HECT domain, promotes K63-linked (non-degradative) ubiquitination of ERα that inhibits K48-linked poly-ubiquitination, thereby increasing ERα stability and facilitating ERα target gene expression in breast cancer cells. Co-immunoprecipitation, domain mapping, ubiquitin linkage assay, protein stability assay, siRNA knockdown, xenograft model Journal of experimental & clinical cancer research Medium 29433542
2015 F-box protein Fbxo3 interacts with Smurf1 and targets it for poly-ubiquitination and proteasomal degradation, unlike FBXL15 which acts selectively on Smurf1, Fbxo3 targets all Nedd4 family members. Co-immunoprecipitation, ubiquitination assay, protein stability assay Biochemical and biophysical research communications Medium 25721664
2016 AMPK activation upregulates Smad6 and Smurf1 and enhances their interaction, leading to proteasome-dependent degradation of constitutively active ALK2 (R206H mutant), thereby inhibiting ectopic osteogenesis. Knockdown of Smad6 or Smurf1 blocks metformin-induced ALK2 reduction. Co-immunoprecipitation, proteasome inhibitor experiments, AMPK dominant-negative/constitutively-active mutants, siRNA knockdown epistasis, FOP patient-derived iPS cell differentiation assay Biochimica et biophysica acta. Molecular cell research Medium 28847510
2014 Smurf1 phosphorylation at S148 by AMPK is required for its function: Smurf1(S148A) knock-in mice exhibit premature osteoblast differentiation equivalent to Smurf1-/- mice, increased insulin signaling due to reduced insulin receptor degradation, and elevated osteocalcin with hypoglycemia. Knock-in mouse model (S148A), Western blotting, osteoblast differentiation assay, insulin signaling analysis Cell reports High 27052174
2018 SMURF1 is expressed at the primary cilium and regulates BMP signaling during cardiac outflow tract septation and cell-type specification in mammalian heart development; Smurf1-/- embryos show delayed outflow tract septation and reduced aortic smooth muscle cell layer thickness. Smurf1-/- mouse embryo analysis, immunofluorescence localization to primary cilium, in vitro differentiation assays Scientific reports Medium 29934521
2021 Smurf1 catalyzes neddylation of RRP9 (a U3 snoRNP component) at K221, which is required for pre-rRNA processing and ribosomal biogenesis. Unneddylatable RRP9 (K221R) fails to promote tumor cell proliferation, colony formation, and migration. In vitro and in vivo neddylation assay, mutagenesis (K221R), pre-rRNA processing assay, tumor cell proliferation/migration assays The Journal of biological chemistry High 34662580
2024 Smurf1 triggers PDK1 neddylation upon growth factor stimulation, and poly-Nedd8 chains on PDK1 recruit SETDB1 methyltransferase. The cytoplasmic complex (cCOMPASS) of PDK1-Smurf1-SETDB1 directs Akt membrane attachment and T308 phosphorylation, activating PI3K-Akt signaling in KRAS-mutated colorectal cancer. Co-immunoprecipitation, in vitro neddylation assay, Smurf1 genetic KO mouse model, PROTAC degrader (Smurf1-antagonizing repressor of tumor 1), Akt phosphorylation and membrane localization assays Nature chemical biology High 39039255
2022 ERK-mediated phosphorylation of Smurf1 at Thr223 is required for Smurf1-mediated RhoA ubiquitination and degradation during TGF-β-induced EMT. Blocking Smurf1 T223 phosphorylation inhibits TGF-β-induced EMT and dramatically reduces lung metastasis in a murine breast cancer model. Phosphorylation assay, site-directed mutagenesis (T223A), ubiquitination assay, EMT marker analysis, in vivo metastasis model Life science alliance High 35654587
2018 SMURF1 ubiquitinates SMURF1-activated MAVS and promotes it for degradation via Ndfip1 adaptor. Additionally, miR-140-5p targets SMURF1 in pulmonary arterial smooth muscle cells; SMURF1 knockdown or miR-140-5p mimic alters BMP signaling, and Smurf1 deletion protects mice from PAH. miR-140-5p mimic delivery in PAH rat models, SMURF1 siRNA knockdown, BMP signaling reporter, Smurf1-/- mouse PAH model The Journal of clinical investigation Medium 27214554
2020 Smurf1 ubiquitylates and degrades PTEN, activating PI3K/Akt/mTOR signaling in glioblastoma. Smurf1 deficiency abolishes aberrant PTEN regulation, re-sensitizes tumor cells to mTOR inhibition (rapamycin), and dramatically reduces CRC/GBM tumorigenesis. Co-immunoprecipitation, ubiquitination assay, Smurf1 knockdown/overexpression, orthotopic GBM mouse model, rapamycin combination treatment Oncogene Medium 32737433
2016 Smurf1 promotes DAB2IP ubiquitination and degradation; Smurf1-mediated cell proliferation and migration are largely dependent on DAB2IP. Akt1/Akt2 phosphorylate Smurf1 to enhance its abundance, leading to further DAB2IP reduction. Co-immunoprecipitation, ubiquitination assay, Akt kinase assay, siRNA knockdown epistasis, cell proliferation/migration assay Oncotarget Medium 27036023
2016 RASSF1A directly interacts with GTP-RhoA via its C-terminal region (aa 256-277) and also binds Smurf1 via its N-terminal region (aa 69-82), facilitating Smurf1-mediated ubiquitination of GTP-RhoA and tumor suppression. RASSF1A mutants unable to bind RhoA or Smurf1 fail to suppress RhoA-induced tumor progression. Co-immunoprecipitation, domain mutagenesis, ubiquitination assay, cell proliferation/migration/invasion assays Cancer research Medium 26825171
2023 Smurf1 interacts with p62 and enhances the liquidity of p62 phase-separated droplets (LLPS), promoting p62-Keap1 competitive binding and Nrf2 nuclear translocation. Smurf1 also activates mTORC1, leading to p62 Ser349 phosphorylation, and maintains autophagic cargo clearance through p62/LC3 pathway. Co-immunoprecipitation, live-cell liquid droplet imaging (LLPS assay), Nrf2 reporter assay, mTORC1 activity assay, autophagy flux analysis Cell & bioscience Medium 36810259
2019 SMURF1 ubiquitinates ARHGAP26 (a RhoA GAP/tumor suppressor), promoting its degradation, which increases active GTP-RhoA levels and activates β-catenin signaling to promote ovarian cancer cell invasion and migration. Co-immunoprecipitation, ubiquitination assay, SMURF1 overexpression, ARHGAP26 overexpression rescue, GTP-RhoA pull-down assay, β-catenin activity measurement, in vivo metastasis assay Experimental & molecular medicine Medium 31004081
2018 Smurf1 protein expression decreases in nucleus accumbens on withdrawal day 7 after cocaine self-administration (not day 1), causing accumulation of its substrates RhoA and Smad1/5. Viral-mediated Smurf1 overexpression or constitutively active RhoA attenuates cue-induced cocaine seeking; catalytically inactive Smurf1 enhances it. Western blot, Co-immunoprecipitation, TUBE affinity purification, chromatin immunoprecipitation, viral-mediated gene transfer, intra-accumbal microinjections Biological psychiatry Medium 30158054
2006 LMP-1 (LIM mineralization protein-1) interacts directly with the Smurf1 WW2 domain via a PY-like motif, competing with Smad1/5 for binding and thereby preventing their ubiquitination, increasing cellular BMP responsiveness. Co-immunoprecipitation, competitive binding assay, ubiquitination assay, peptide competition experiment The Journal of biological chemistry Medium 16611643

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Ubiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation. Cell 310 15820682
2003 Cooperative inhibition of bone morphogenetic protein signaling by Smurf1 and inhibitory Smads. Molecular biology of the cell 266 12857866
2005 Tumor necrosis factor promotes Runx2 degradation through up-regulation of Smurf1 and Smurf2 in osteoblasts. The Journal of biological chemistry 261 16373342
2003 E3 ubiquitin ligase Smurf1 mediates core-binding factor alpha1/Runx2 degradation and plays a specific role in osteoblast differentiation. The Journal of biological chemistry 242 12738770
2014 The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis. Nature communications 185 24821572
2016 The Ubiquitin Ligase Smurf1 Functions in Selective Autophagy of Mycobacterium tuberculosis and Anti-tuberculous Host Defense. Cell host & microbe 180 28017659
2009 Talin phosphorylation by Cdk5 regulates Smurf1-mediated talin head ubiquitylation and cell migration. Nature cell biology 172 19363486
2003 Smurf1 inhibits osteoblast differentiation and bone formation in vitro and in vivo. The Journal of biological chemistry 169 14701828
2006 Smurf1 regulates tumor cell plasticity and motility through degradation of RhoA leading to localized inhibition of contractility. The Journal of cell biology 157 17190792
2008 Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1. Nature cell biology 136 18641638
2011 Phosphorylation of E3 ligase Smurf1 switches its substrate preference in support of axon development. Neuron 127 21262463
2016 MicroRNA-140-5p and SMURF1 regulate pulmonary arterial hypertension. The Journal of clinical investigation 126 27214554
2008 Ubiquitin ligase Smurf1 mediates tumor necrosis factor-induced systemic bone loss by promoting proteasomal degradation of bone morphogenetic signaling proteins. The Journal of biological chemistry 114 18567580
2012 Ndfip1 negatively regulates RIG-I-dependent immune signaling by enhancing E3 ligase Smurf1-mediated MAVS degradation. Journal of immunology (Baltimore, Md. : 1950) 112 23087404
2019 Ubiquitination of UVRAG by SMURF1 promotes autophagosome maturation and inhibits hepatocellular carcinoma growth. Autophagy 106 30686098
2012 Deubiquitinase FAM/USP9X interacts with the E3 ubiquitin ligase SMURF1 protein and protects it from ligase activity-dependent self-degradation. The Journal of biological chemistry 101 23184937
2011 Cdh1 regulates osteoblast function through an APC/C-independent modulation of Smurf1. Molecular cell 94 22152476
2015 SND1 Acts Downstream of TGFβ1 and Upstream of Smurf1 to Promote Breast Cancer Metastasis. Cancer research 86 25596283
2012 A Smurf1 tale: function and regulation of an ubiquitin ligase in multiple cellular networks. Cellular and molecular life sciences : CMLS 84 23007848
2008 Smurf2 induces ubiquitin-dependent degradation of Smurf1 to prevent migration of breast cancer cells. The Journal of biological chemistry 83 18927080
2010 Smurf1 inhibits mesenchymal stem cell proliferation and differentiation into osteoblasts through JunB degradation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 81 20200942
2014 Selective small molecule compounds increase BMP-2 responsiveness by inhibiting Smurf1-mediated Smad1/5 degradation. Scientific reports 75 24828823
2019 miR-1254 inhibits cell proliferation, migration, and invasion by down-regulating Smurf1 in gastric cancer. Cell death & disease 72 30631050
2003 Smurf1 facilitates myogenic differentiation and antagonizes the bone morphogenetic protein-2-induced osteoblast conversion by targeting Smad5 for degradation. The Journal of biological chemistry 71 12871975
2018 MicroRNA-424(322) as a new marker of disease progression in pulmonary arterial hypertension and its role in right ventricular hypertrophy by targeting SMURF1. Cardiovascular research 70 29016730
2010 Smad ubiquitylation regulatory factor 1/2 (Smurf1/2) promotes p53 degradation by stabilizing the E3 ligase MDM2. The Journal of biological chemistry 67 20484049
2003 Chromosomal region maintenance 1 (CRM1)-dependent nuclear export of Smad ubiquitin regulatory factor 1 (Smurf1) is essential for negative regulation of transforming growth factor-beta signaling by Smad7. The Journal of biological chemistry 66 12519765
2011 The E3 ligase Smurf1 regulates Wolfram syndrome protein stability at the endoplasmic reticulum. The Journal of biological chemistry 63 21454619
2015 The p53/miR-17/Smurf1 pathway mediates skeletal deformities in an age-related model via inhibiting the function of mesenchymal stem cells. Aging 61 25855145
2012 Up-regulation of BMP-2 antagonizes TGF-β1/ROCK-enhanced cardiac fibrotic signalling through activation of Smurf1/Smad6 complex. Journal of cellular and molecular medicine 61 22283839
2017 MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression. Scientific reports 56 28341855
2009 Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination and degradation. Molecular and cellular biochemistry 56 19937093
2016 Smurf1 Inhibits Osteoblast Differentiation, Bone Formation, and Glucose Homeostasis through Serine 148. Cell reports 55 27052174
2011 SCFFBXL¹⁵ regulates BMP signalling by directing the degradation of HECT-type ubiquitin ligase Smurf1. The EMBO journal 55 21572392
2006 CNF1-induced ubiquitylation and proteasome destruction of activated RhoA is impaired in Smurf1-/- cells. Molecular biology of the cell 55 16540523
2006 LIM mineralization protein-1 potentiates bone morphogenetic protein responsiveness via a novel interaction with Smurf1 resulting in decreased ubiquitination of Smads. The Journal of biological chemistry 54 16611643
2006 FKBP12 functions as an adaptor of the Smad7-Smurf1 complex on activin type I receptor. Journal of molecular endocrinology 54 16720724
2019 Bortezomib attenuates renal interstitial fibrosis in kidney transplantation via regulating the EMT induced by TNF-α-Smurf1-Akt-mTOR-P70S6K pathway. Journal of cellular and molecular medicine 52 31140729
2005 Ubiquitination of RhoA by Smurf1 promotes neurite outgrowth. FEBS letters 52 15710384
2017 CKIP-1 affects the polyubiquitination of Nrf2 and Keap1 via mediating Smurf1 to resist HG-induced renal fibrosis in GMCs and diabetic mice kidneys. Free radical biology & medicine 51 29248720
2020 Bone Marrow Mesenchymal Stem Cell-Derived Exosomal miR-25 Regulates the Ubiquitination and Degradation of Runx2 by SMURF1 to Promote Fracture Healing in Mice. Frontiers in medicine 50 33425934
2018 Inhibition of osteoblastic Smurf1 promotes bone formation in mouse models of distinctive age-related osteoporosis. Nature communications 50 30143635
2014 TRIB2 inhibits Wnt/β-Catenin/TCF4 signaling through its associated ubiquitin E3 ligases, β-TrCP, COP1 and Smurf1, in liver cancer cells. FEBS letters 50 25311538
2010 Smurf1 ubiquitin ligase causes downregulation of BMP receptors and is induced in monocrotaline and hypoxia models of pulmonary arterial hypertension. Experimental biology and medicine (Maywood, N.J.) 50 20558834
2022 The mechanosensitive lncRNA Neat1 promotes osteoblast function through paraspeckle-dependent Smurf1 mRNA retention. Bone research 49 35210394
2019 Knockdown of long noncoding RNA XIST mitigates the apoptosis and inflammatory injury of microglia cells after spinal cord injury through miR-27a/Smurf1 axis. Neuroscience letters 47 31778769
2017 TGF-β inhibits osteogenesis by upregulating the expression of ubiquitin ligase SMURF1 via MAPK-ERK signaling. Journal of cellular physiology 47 28322449
2018 SMURF1 facilitates estrogen receptor ɑ signaling in breast cancer cells. Journal of experimental & clinical cancer research : CR 46 29433542
2017 SMURF1 promotes the proliferation, migration and invasion of gastric cancer cells. Oncology reports 45 28731194
2013 Ubiquitination of tumor necrosis factor receptor-associated factor 4 (TRAF4) by Smad ubiquitination regulatory factor 1 (Smurf1) regulates motility of breast epithelial and cancer cells. The Journal of biological chemistry 45 23760265
2020 LncRNA SNHG3 sponges miR-577 to up-regulate SMURF1 expression in prostate cancer. Cancer medicine 44 32248648
2017 Smurf1 inhibits integrin activation by controlling Kindlin-2 ubiquitination and degradation. The Journal of cell biology 43 28408404
2011 Pivotal role of the C2 domain of the Smurf1 ubiquitin ligase in substrate selection. The Journal of biological chemistry 43 21402695
2004 Overexpression of Smurf1 negatively regulates mouse embryonic lung branching morphogenesis by specifically reducing Smad1 and Smad5 proteins. American journal of physiology. Lung cellular and molecular physiology 43 14711801
2018 USF2 inhibits the transcriptional activity of Smurf1 and Smurf2 to promote breast cancer tumorigenesis. Cellular signalling 41 30244169
2014 ATR/Chk1/Smurf1 pathway determines cell fate after DNA damage by controlling RhoB abundance. Nature communications 41 25249323
2013 SMURF1 plays a role in EGF-induced breast cancer cell migration and invasion. Molecules and cells 41 24241683
2011 Smurf1 ubiquitin ligase targets Kruppel-like factor KLF2 for ubiquitination and degradation in human lung cancer H1299 cells. Biochemical and biophysical research communications 40 21382345
2017 The Role of Smurf1 in Neuronal Necroptosis after Lipopolysaccharide-Induced Neuroinflammation. Cellular and molecular neurobiology 39 28940129
2008 Smurf1 directly targets hPEM-2, a GEF for Cdc42, via a novel combination of protein interaction modules in the ubiquitin-proteasome pathway. Biological chemistry 39 18208356
2020 microRNA-148a-3p in extracellular vesicles derived from bone marrow mesenchymal stem cells suppresses SMURF1 to prevent osteonecrosis of femoral head. Journal of cellular and molecular medicine 38 32871042
2013 CKIP-1 acts as a colonic tumor suppressor by repressing oncogenic Smurf1 synthesis and promoting Smurf1 autodegradation. Oncogene 38 23995790
2004 Smurf1: a link between cell polarity and ubiquitination. Cell cycle (Georgetown, Tex.) 36 14752271
2020 Oncogenic Smurf1 promotes PTEN wild-type glioblastoma growth by mediating PTEN ubiquitylation. Oncogene 35 32737433
2015 CD166 positively regulates MCAM via inhibition to ubiquitin E3 ligases Smurf1 and βTrCP through PI3K/AKT and c-Raf/MEK/ERK signaling in Bel-7402 hepatocellular carcinoma cells. Cellular signalling 35 26004137
2010 HECT ubiquitin ligase Smurf1 targets the tumor suppressor ING2 for ubiquitination and degradation. FEBS letters 35 20621832
2020 TGFβ1 Suppressed Matrix Mineralization of Osteoblasts Differentiation by Regulating SMURF1-C/EBPβ-DKK1 Axis. International journal of molecular sciences 34 33371439
2019 miR-4319 inhibited the development of thyroid cancer by modulating FUS-stabilized SMURF1. Journal of cellular biochemistry 34 31148243
2014 Bortezomib prevents oncogenesis and bone metastasis of prostate cancer by inhibiting WWP1, Smurf1 and Smurf2. International journal of oncology 34 25051198
2020 IMP3 accelerates the progression of prostate cancer through inhibiting PTEN expression in a SMURF1-dependent way. Journal of experimental & clinical cancer research : CR 31 32938489
2020 MiRNA-516a promotes bladder cancer metastasis by inhibiting MMP9 protein degradation via the AKT/FOXO3A/SMURF1 axis. Clinical and translational medicine 31 33377649
2019 SMURF1-mediated ubiquitination of ARHGAP26 promotes ovarian cancer cell invasion and migration. Experimental & molecular medicine 31 31004081
2018 Intracellular attenuation of BMP signaling via CKIP-1/Smurf1 is essential during neural crest induction. PLoS biology 31 29949573
2016 RASSF1A Directly Antagonizes RhoA Activity through the Assembly of a Smurf1-Mediated Destruction Complex to Suppress Tumorigenesis. Cancer research 31 26825171
2010 REGgamma proteasome mediates degradation of the ubiquitin ligase Smurf1. FEBS letters 31 20580715
2019 MicroRNA-424 regulates cisplatin resistance of gastric cancer by targeting SMURF1 based on GEO database and primary validation in human gastric cancer tissues. OncoTargets and therapy 30 31571913
2018 Smurf1 regulates macrophage proliferation, apoptosis and migration via JNK and p38 MAPK signaling pathways. Molecular immunology 30 29550577
2017 AMPK downregulates ALK2 via increasing the interaction between Smurf1 and Smad6, leading to inhibition of osteogenic differentiation. Biochimica et biophysica acta. Molecular cell research 30 28847510
2008 Identification of SMURF1 as a possible target for 7q21.3-22.1 amplification detected in a pancreatic cancer cell line by in-house array-based comparative genomic hybridization. Cancer science 30 18380791
2021 FOSL1 promotes tumorigenesis in colorectal carcinoma by mediating the FBXL2/Wnt/β-catenin axis via Smurf1. Pharmacological research 29 33450386
2016 Smurf1 regulation of DAB2IP controls cell proliferation and migration. Oncotarget 29 27036023
2019 SND1 facilitates the invasion and migration of cervical cancer cells by Smurf1-mediated degradation of FOXA2. Experimental cell research 26 31891682
2018 The E3 ubiquitin ligase SMURF1 regulates cell-fate specification and outflow tract septation during mammalian heart development. Scientific reports 26 29934521
2020 SMURF1, a promoter of tumor cell progression? Cancer gene therapy 25 33204002
2018 Role of SMURF1 ubiquitin ligase in BMP receptor trafficking and signaling. Cellular signalling 24 30395943
2018 Non-proteolytic ubiquitin modification of PPARγ by Smurf1 protects the liver from steatosis. PLoS biology 24 30566427
2015 F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Biochemical and biophysical research communications 24 25721664
2010 Identification of substrates of SMURF1 ubiquitin ligase activity utilizing protein microarrays. Assay and drug development technologies 24 20804422
2023 Enhanced liquidity of p62 droplets mediated by Smurf1 links Nrf2 activation and autophagy. Cell & bioscience 23 36810259
2021 Neddylation modification of the U3 snoRNA-binding protein RRP9 by Smurf1 promotes tumorigenesis. The Journal of biological chemistry 23 34662580
2017 Uev1A facilitates osteosarcoma differentiation by promoting Smurf1-mediated Smad1 ubiquitination and degradation. Cell death & disease 23 28771228
2024 Targeting Smurf1 to block PDK1-Akt signaling in KRAS-mutated colorectal cancer. Nature chemical biology 22 39039255
2022 ERK-Smurf1-RhoA signaling is critical for TGFβ-drived EMT and tumor metastasis. Life science alliance 22 35654587
2021 JAC1 suppresses proliferation of breast cancer through the JWA/p38/SMURF1/HER2 signaling. Cell death discovery 22 33875644
2016 Transcription factor Six2 mediates the protection of GDNF on 6-OHDA lesioned dopaminergic neurons by regulating Smurf1 expression. Cell death & disease 22 27148690
2014 A feedback loop between RUNX2 and the E3 ligase SMURF1 in regulation of differentiation of human dental pulp stem cells. Journal of endodontics 22 25260729
2012 p250GAP is a novel player in the Cdh1-APC/Smurf1 pathway of axon growth regulation. PloS one 22 23226367
2006 Smurf1 regulates neural patterning and folding in Xenopus embryos by antagonizing the BMP/Smad1 pathway. Developmental biology 22 16973150
2018 E3 Ubiquitin-Protein Ligase SMURF1 in the Nucleus Accumbens Mediates Cocaine Seeking. Biological psychiatry 21 30158054
2014 Smurf1-mediated axin ubiquitination requires Smurf1 C2 domain and is cell cycle-dependent. The Journal of biological chemistry 21 24700460