Affinage

SMURF1

E3 ubiquitin-protein ligase SMURF1 · UniProt Q9HCE7

Length
757 aa
Mass
86.1 kDa
Annotated
2026-06-10
100 papers in source corpus 54 papers cited in narrative 54 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

SMURF1 is a HECT-domain E3 ubiquitin ligase that governs cellular responses to the BMP/TGF-β family, cell polarity and migration, and several metabolic and immune programs by selectively ubiquitinating signaling proteins (PMID:11278251, PMID:15820682). Its founding activity is the negative regulation of TGF-β/BMP signaling: SMURF1 binds the inhibitory Smad7, ubiquitinates it, and uses it as an adaptor to recruit and degrade the type I receptor, and it cooperates with inhibitory Smads to degrade BMP receptors and Smad1/5, thereby antagonizing osteoblastic differentiation and patterning (PMID:11278251, PMID:12857866, PMID:12871975). A C2 domain provides membrane targeting and substrate selection — it is required to localize the SMURF1–Smad7 complex to the plasma membrane and is necessary and sufficient to bind substrates such as RhoA and Axin, while the WW domains capture PY-motif substrates and the HECT domain catalyzes transfer (PMID:12151385, PMID:21402695, PMID:21708152). SMURF1 controls cell motility by degrading active RhoA locally to limit ROCK/MLC2 signaling and enable lamellipodial protrusion (PMID:16540523, PMID:17190792), and it shapes adhesion through degradation of talin head and Kindlin-2 (PMID:19363486, PMID:28408404). Beyond canonical degradative ubiquitination, SMURF1 installs non-proteolytic chains: K29-linked ubiquitination of Axin disrupts LRP6 coupling to repress Wnt/β-catenin signaling, K63-linked ubiquitination of PPARγ suppresses its transcription to restrain hepatic lipid accumulation, and K29/K33-linked ubiquitination of UVRAG promotes autophagosome maturation (PMID:23959799, PMID:30566427, PMID:30686098). SMURF1 is also required for selective autophagy of intracellular Mycobacterium tuberculosis and attenuates antiviral and cytokine signaling by degrading MAVS and STAT1 (PMID:28017659, PMID:23087404, PMID:22474288). The enzyme is auto-activated by neddylation through an active-site cysteine (C426), and additionally acts as a Nedd8 ligase toward substrates: it neddylates RRP9 to promote ribosome biogenesis and neddylates PDK1 to assemble a cytoplasmic PDK1–SMURF1–SETDB1 complex driving Akt activation and KRAS-mutant tumorigenesis (PMID:24821572, PMID:34662580, PMID:39039255). SMURF1 activity is tuned by co-factors (CKIP-1, Cdh1) and by kinase inputs — PKA phosphorylation at Thr306, ERK at Thr223, AMPK at Ser148, and ATR/Chk1 — that switch substrate preference or trigger self-degradation (PMID:18641638, PMID:22152476, PMID:21262463, PMID:35654587, PMID:27052174, PMID:25249323).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2001 High

    Established the founding function of SMURF1 as a negative regulator of TGF-β signaling by showing it ubiquitinates Smad7 and uses it to target the type I receptor.

    Evidence Co-IP and ubiquitination assays in mammalian cells

    PMID:11278251

    Open questions at the time
    • Did not define the ubiquitin chain linkage
    • Did not address regulation of SMURF1 activity itself
  2. 2002 High

    Identified the C2 domain as the membrane-targeting module required for receptor recruitment, answering how the ligase reaches its membrane substrates.

    Evidence C2-deletion mutants with localization, Co-IP, and ubiquitination assays

    PMID:12151385

    Open questions at the time
    • Structural basis of C2 membrane/substrate binding not resolved here
    • Did not test C2 role for non-receptor substrates
  3. 2003 High

    Extended the inhibitory repertoire to BMP receptors and the osteoblast transcription factor Runx2, placing SMURF1 at the center of bone/skeletal differentiation control.

    Evidence Xenopus axis and reporter assays, Co-IP and ubiquitination in osteoblast precursors, Smad5-selective degradation with rescue

    PMID:12738770 PMID:12857866 PMID:12871975

    Open questions at the time
    • Selectivity determinants distinguishing Smad5 from Smad2/3 not mapped
    • In vivo bone consequence not yet shown in these reports
  4. 2005 High

    Genetic loss-of-function defined SMURF1 as a physiological suppressor of osteoblast activity and revealed a Smad-independent axis through MEKK2/JNK.

    Evidence Smurf1-knockout mice with bone phenotype, Co-IP, in vitro ubiquitination, and JNK epistasis; RhoA degradation shown in neurons

    PMID:15710384 PMID:15820682

    Open questions at the time
    • How SMURF1 partitions between Smad and MEKK2 substrates in vivo unclear
    • Upstream signals selecting MEKK2 not defined
  5. 2006 High

    Defined SMURF1 as the rate-limiting, specific E3 for activated RhoA and linked this to localized cytoskeletal control of migration and invasion.

    Evidence Smurf1-KO cells with rescue, CNF1 activation, ROCK/MLC2 readouts, 2D/3D invasion and in vivo migration assays

    PMID:16540523 PMID:17190792

    Open questions at the time
    • Spatial mechanism restricting RhoA degradation to the cell periphery not fully resolved
    • Determinants of active- versus inactive-RhoA recognition unclear
  6. 2008 High

    Identified co-factor and cross-regulatory control of SMURF1 activity, showing CKIP-1 augments its ligase activity and Smurf2 degrades it.

    Evidence Co-IP, domain mapping, in vitro ubiquitination, and CKIP-1 knockout mouse bone phenotype

    PMID:18641638 PMID:18927080

    Open questions at the time
    • Mechanism by which CKIP-1 increases catalytic output not structurally defined
    • Physiological trigger for Smurf2-mediated SMURF1 turnover unknown
  7. 2009 High

    Showed SMURF1 controls focal-adhesion turnover by degrading the calpain-generated talin head, and that Cdk5 phosphorylation of talin protects it, integrating proteolysis into adhesion dynamics.

    Evidence Co-IP, in vitro ubiquitination, kinase assay, phospho-mutants, focal adhesion and migration assays

    PMID:19363486

    Open questions at the time
    • Whether full-length talin is ever a substrate in vivo unclear
    • Coordination with RhoA-directed activity during migration not addressed
  8. 2011 High

    Provided structural and mechanistic dissection: the C2 domain mediates substrate selection (RhoA, Axin) rather than Smurf2-type autoinhibition, and Cdh1 activates SMURF1 by disrupting an autoinhibitory homodimer.

    Evidence C2 crystal structure with mutagenesis, FRET, ubiquitination assays, and Cdh1 homodimer-disruption and osteoblast differentiation readouts; SCF(FBXL15) shown to degrade SMURF1

    PMID:21402695 PMID:21572392 PMID:21708152 PMID:22152476

    Open questions at the time
    • Full-length SMURF1 structure and chain-type determinants not resolved
    • How Cdh1 and CKIP-1 inputs are integrated unclear
  9. 2011 High

    Revealed PKA phosphorylation at Thr306 as a substrate-preference switch directing SMURF1 toward RhoA over Par6 to control neuronal polarization.

    Evidence PKA kinase assay, phospho-mutants, in vitro ubiquitination, neuronal axon-formation assay, in utero electroporation

    PMID:21262463

    Open questions at the time
    • Structural basis of phospho-driven substrate switching not defined
    • Other kinases acting at the same site not yet identified
  10. 2012 High

    Connected SMURF1 to antiviral and cytokine signaling by degrading MAVS (with Ndfip1) and K48-ubiquitinating STAT1, and identified USP9X as a stabilizing deubiquitinase.

    Evidence Co-IP, linkage-specific ubiquitination, siRNA, IFN reporters, and mass-spectrometry interactomics

    PMID:22474288 PMID:23087404 PMID:23184937

    Open questions at the time
    • In vivo immune phenotypes of these substrate relationships not established here
    • Balance between USP9X protection and Smurf2/FBXL15 turnover unclear
  11. 2013 High

    Demonstrated that SMURF1 builds non-degradative ubiquitin chains — K29-linked on Axin to repress Wnt and K190 on TRAF4 for localization — expanding its output beyond proteasomal degradation.

    Evidence Linkage-specific and site-specific ubiquitination assays, mutagenesis, Wnt reporters, Smurf1-KO MEFs, Rac1 activation and migration assays

    PMID:23760265 PMID:23959799

    Open questions at the time
    • How SMURF1 selects chain linkage per substrate is unknown
    • Readers decoding the K29 Axin chain not identified
  12. 2014 High

    Identified neddylation as a core regulatory mechanism: SMURF1 auto-neddylates via C426 to boost E2 recruitment and ligase activity, and DNA-damage Chk1 signaling drives SMURF1 self-degradation to permit RhoB-dependent apoptosis.

    Evidence Reconstituted in vitro neddylation, thioester trapping, active-site mutagenesis, yeast Rsp5 conservation; kinase assays and phospho-mutants for the Chk1 axis

    PMID:24821572 PMID:25249323

    Open questions at the time
    • Endogenous triggers of SMURF1 auto-neddylation in cells not defined
    • Phospho-sites mediating Chk1-driven self-degradation not fully mapped
  13. 2016 High

    Established SMURF1 as a mediator of selective xenophagy and an AMPK-controlled metabolic node, requiring its C2 and ligase domains for anti-mycobacterial autophagy and Ser148 phosphorylation for osteoblast/insulin-receptor control.

    Evidence Smurf1-/- macrophages and infection in mice, domain and linkage analysis; Smurf1 S148A knock-in mouse with bone and glucose phenotypes

    PMID:27052174 PMID:28017659

    Open questions at the time
    • Direct ubiquitinated cargo on Mtb-associated structures not fully defined
    • How AMPK phosphorylation alters catalytic behavior mechanistically unclear
  14. 2018 High

    Defined a metabolic role through non-degradative K63 ubiquitination of PPARγ, with Smurf1 loss causing hepatic steatosis reversible by PPARγ antagonism.

    Evidence Smurf1-KO mouse, K63-linkage-specific ubiquitination, PPARγ reporter, pharmacological rescue, high-fat diet

    PMID:30566427

    Open questions at the time
    • Tissue-specific contribution of SMURF1 to lipid metabolism not dissected
    • Coordination with other PPARγ regulators unknown
  15. 2019 High

    Showed SMURF1 promotes autophagosome maturation by K29/K33-ubiquitinating UVRAG, with kinase and DUB inputs (CSNK1A1, ZRANB1) gating the modification.

    Evidence Co-IP, site-specific and linkage-determined ubiquitination, autophagosome maturation, kinase and deubiquitinase assays

    PMID:30686098

    Open questions at the time
    • How UVRAG ubiquitination integrates with the xenophagy role unclear
    • Structural recognition of UVRAG sites not resolved
  16. 2021 High

    Expanded SMURF1 to a bona fide Nedd8 ligase by showing it neddylates RRP9 to promote pre-rRNA processing and ribosome biogenesis.

    Evidence In vivo/in vitro neddylation, K221R mutagenesis, pre-rRNA processing assay, NEDP1 deneddylation, tumor proliferation assays

    PMID:34662580

    Open questions at the time
    • Determinants distinguishing ubiquitin versus Nedd8 transfer not defined
    • Scope of the SMURF1 neddylome unknown
  17. 2022 High

    Identified ERK phosphorylation at Thr223 as a TGFβ-induced prerequisite for RhoA degradation, EMT, and metastasis, providing a druggable kinase–ligase link.

    Evidence Kinase assay, phospho-mutants, Co-IP, ubiquitination, EMT markers, in vivo lung metastasis

    PMID:35654587

    Open questions at the time
    • Interplay between Thr223 (ERK) and Thr306 (PKA) phospho-control not resolved
    • Whether other migration substrates respond to Thr223 status unknown
  18. 2024 High

    Linked SMURF1 neddylase activity to oncogenic Akt signaling: PDK1 neddylation assembles a cytoplasmic PDK1–SMURF1–SETDB1 complex driving Akt activation, and a SMURF1 degrader suppresses KRAS-mutant tumors.

    Evidence In vitro neddylation, complex identification, Smurf1-KO CRC mouse model, Akt membrane-recruitment assay, PROTAC degrader

    PMID:39039255

    Open questions at the time
    • How SETDB1 methyltransferase activity contributes mechanistically unclear
    • Selectivity and broader effects of the degrader not fully characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how SMURF1 selects between proteasomal versus non-degradative chain linkages and between ubiquitin versus Nedd8 transfer for a given substrate, and how its many kinase and co-factor inputs are integrated on a single full-length enzyme.
  • No full-length structure capturing substrate, co-factor, and chain-type selection
  • No unified model reconciling competing phospho-inputs (PKA/ERK/AMPK/Chk1)
  • Determinants of ubiquitin-versus-Nedd8 cofactor choice undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0008289 lipid binding 3 GO:0016874 ligase activity 3 GO:0031386 protein tag activity 3
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 2 GO:0005929 cilium 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-1430728 Metabolism 2 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 2
Partners
AXIN1CKIP-1MEKK2RHOASMAD7TRAF4USP9XUVRAG
Complex memberships
PDK1-SMURF1-SETDB1 (cCOMPASS)

Evidence

Reading pass · 54 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Smurf1 physically interacts with Smad7 and induces Smad7 ubiquitination and translocation from nucleus to cytoplasm; Smurf1 then associates with TGF-β type I receptor (TβR-I) via Smad7 as an adaptor, leading to enhanced proteasomal turnover of both TβR-I and Smad7. Co-immunoprecipitation, ubiquitination assays, overexpression in mammalian cells The Journal of biological chemistry High 11278251
2002 The C2 domain of Smurf1 is required to target the Smurf1-Smad7 complex to the plasma membrane; deletion of the C2 domain prevents plasma membrane localization, blocks recruitment of Smad7 to the TβR-II/TβR-I complex, and abolishes TβR-I ubiquitination and degradation as well as Smad7 inhibitory activity. C2-domain deletion mutant analysis, subcellular localization by microscopy, Co-IP, ubiquitination assay The Journal of biological chemistry High 12151385
2003 Smurf1 cooperates with inhibitory Smads (Smad6/7) to ubiquitinate and degrade BMP type I receptors; Smurf1 can also ubiquitinate Smad1/5 indirectly through I-Smads, expanding its inhibitory repertoire beyond direct Smad binding. Xenopus secondary axis assay, BMP-responsive reporter assay, ubiquitination assay, Co-IP Molecular biology of the cell High 12857866
2003 Smurf1 directly interacts with the osteoblast-specific transcription factor Runx2/Cbfa1 and mediates its ubiquitin- and proteasome-dependent degradation, controlling osteoblast differentiation. Co-IP, ubiquitination assay, proteasome inhibitor experiments, overexpression in osteoblast precursor cells The Journal of biological chemistry High 12738770
2003 Increased Smurf1 expression promotes myogenic differentiation of C2C12 cells and blocks BMP-induced osteogenic conversion by selectively reducing endogenous Smad5 levels while leaving TGF-β-pathway Smads (Smad2, 3, 7) unaffected; siRNA-mediated depletion of endogenous Smurf1 is required for normal myogenic differentiation. Overexpression, siRNA knockdown, Western blot, Smad5 rescue experiment The Journal of biological chemistry High 12871975
2003 Transgenic overexpression of Smurf1 in osteoblasts (under type I collagen promoter) significantly reduces bone formation in vivo, demonstrating a direct in vivo role for Smurf1 in suppressing osteoblast activity through BMP/Smad signaling components. Transgenic mouse generation, bone histomorphometry The Journal of biological chemistry Medium 14701828
2005 Smurf1-deficient mice develop age-dependent bone mass increase due to enhanced osteoblast activity; mechanistically, Smurf1 physically interacts with MEKK2 and promotes its ubiquitination and proteasomal degradation, thereby suppressing downstream JNK signaling in osteoblasts independently of canonical Smad-mediated BMP/TGF-β signaling. Smurf1-knockout mice, Co-IP, in vitro ubiquitination assay, JNK pathway analysis Cell High 15820682
2005 Smurf1 ubiquitinates RhoA and physically interacts with it in neuroblastoma cells; overexpression of Smurf1 selectively reduces RhoA protein levels during cAMP-induced (but not retinoic acid-induced) neurite outgrowth, promoting neurite extension. Co-IP, ubiquitination assay, proteasome inhibitor, Neuro2a neurite outgrowth assay FEBS letters Medium 15710384
2005 TNF-α up-regulates Smurf1 and Smurf2 expression in osteoblasts and promotes proteasomal degradation of Runx2, an effect blocked by siRNA against Smurf1, establishing that TNF-mediated Runx2 degradation requires Smurf1. siRNA knockdown, Western blot, proteasome inhibitor, reporter assay, in vivo TNF transgenic mice The Journal of biological chemistry High 16373342
2006 Using Smurf1-deficient cells and siRNA knockdown, Smurf1 is identified as a rate-limiting, specific factor for ubiquitin-mediated proteasomal degradation of activated (CNF1-constitutively active) RhoA; ectopic Smurf1 restores RhoA ubiquitylation in Smurf1-deficient Vero cells. Smurf1-KO cells, siRNA, CNF1 toxin treatment, ubiquitination assay, rescue by ectopic Smurf1 Molecular biology of the cell High 16540523
2006 Smurf1-mediated RhoA degradation at the cell periphery reduces ROCK activity and myosin light chain 2 (MLC2) phosphorylation locally, enabling lamellipodia formation and 2D tumor cell motility; in 3D invasion, Smurf1 inhibition induces amoeboid-like transition and more invasive behavior. Smurf1 siRNA, ROCK activity assay, MLC2 phosphorylation, 2D and 3D invasion assays, in vivo tumor migration The Journal of cell biology High 17190792
2006 FKBP12 acts as an adaptor for the Smad7-Smurf1 complex on the activin type I receptor (ALK4); FK506, which dissociates FKBP12 from the receptor, decreases Smad7-Smurf1 interaction and inhibits TβR-I ubiquitination by Smurf1. Co-IP, ubiquitination assay, FK506 pharmacological interference Journal of molecular endocrinology Medium 16720724
2006 LMP-1 interacts with the WW2 domain of Smurf1 via a PPxY-like motif and competes with Smad1/5 for Smurf1 binding, blocking ubiquitination of Smads and increasing BMP responsiveness. Co-IP, ubiquitination assay, competitive binding/peptide competition The Journal of biological chemistry Medium 16611643
2006 Smurf1 regulates neural patterning in Xenopus embryos by ubiquitin-mediated degradation of Smad1; morpholino-mediated Smurf1 knockdown elevates phospho-Smad1 levels in dorsal ectoderm and disrupts neural folding, placing Smurf1 as an antagonist of BMP/Smad1 signaling required for neural development. Antisense morpholino knockdown, dominant-negative protein, phospho-Smad1 Western blot, Xenopus embryology Developmental biology Medium 16973150
2008 Smurf2 interacts with Smurf1 and induces its ubiquitination and proteasomal degradation (but not vice versa), providing a post-translational mechanism for cross-regulation between these two related E3 ligases. Co-IP, ubiquitination assay, Western blot after Smurf2 knockdown The Journal of biological chemistry Medium 18927080
2008 CKIP-1 specifically interacts with the linker region between the WW domains of Smurf1 (not Smurf2) and augments Smurf1's E3 ligase activity and substrate affinity; CKIP-1-deficient mice show age-dependent bone mass increase due to reduced Smurf1 activity. Co-IP, in vitro ubiquitination assay, domain mapping, CKIP-1 knockout mouse Nature cell biology High 18641638
2008 Smurf1 interacts with hPEM-2 (a GEF for Cdc42) via a Ca2+-independent C2 domain interaction (mapped to residues 318–343 of the PH domain of hPEM-2) and induces its proteasomal degradation. GST pull-down, pulse-chase labeling, proteasome inhibitor, domain mapping Biological chemistry Medium 18208356
2009 Talin head (generated by calpain cleavage of talin) binds Smurf1 more tightly than full-length talin and is ubiquitylated by Smurf1 leading to its degradation; Cdk5 phosphorylates talin head at Ser425, which inhibits Smurf1 binding and prevents its degradation, thereby stabilizing focal adhesions and supporting cell migration. Co-IP, in vitro ubiquitination assay, kinase assay, phospho-mimetic/phospho-resistant mutants, focal adhesion assays, cell migration assay Nature cell biology High 19363486
2009 Smurf1 interacts with TRAF4 via TRAF4's PY motifs and the second WW domain of Smurf1, promoting ubiquitination and degradation of TRAF4; Smurf1 can ubiquitinate all six TRAF family members and thereby attenuates NF-κB signaling. Yeast two-hybrid, Co-IP, ubiquitination assay, NF-κB reporter Molecular and cellular biochemistry Medium 19937093
2010 Smurf1 interacts with JunB via its PY motif and targets JunB for ubiquitination and proteasomal degradation; Smurf1-deficient MSCs have elevated JunB, increased cyclin D1, and enhanced osteoblast differentiation, placing Smurf1-JunB in a pathway controlling MSC proliferation. Co-IP, ubiquitination assay, Smurf1-KO cells, JunB knockdown/rescue Journal of bone and mineral research High 20200942
2011 The C2 domain of Smurf1 is necessary and sufficient to bind RhoA and is required for RhoA ubiquitination; the C2 domain is dispensable for Smad1 ubiquitination, revealing a substrate-selective role of the C2 domain. Two key lysines (K28 and K85) in the C2 domain are critical for plasma membrane localization and robust RhoA-directed ligase activity. Domain deletion/point mutants, GST pull-down, ubiquitination assay, crystal structure of C2 domain, cell migration assay The Journal of biological chemistry High 21402695
2011 The C2 domain of Smurf1 is necessary and sufficient to bind RhoA (and also Axin), while the C2-HECT autoinhibitory mechanism observed in Smurf2 does not operate in Smurf1; instead, Smurf1's C2 domain functions in substrate selection rather than autoinhibition. FRET, Co-IP, domain deletion mutants, ubiquitination assay FEBS letters Medium 21708152
2011 Cdh1 (APC/C adaptor) promotes Smurf1 E3 ligase activity independently of APC/C E3 activity by disrupting an autoinhibitory Smurf1 homodimer; Cdh1 depletion reduces Smurf1 activity, leading to MEKK2 accumulation and JNK activation, which drives osteoblast differentiation. Co-IP, in vitro ubiquitination assay, siRNA, homodimer disruption assay, osteoblast differentiation readout Molecular cell High 22152476
2011 The SCF(FBXL15) ubiquitin ligase complex targets Smurf1 for ubiquitination and proteasomal degradation; FBXL15 specifically recognizes the HECT domain N-lobe of Smurf1 and ubiquitinates it at K355/K357, thereby positively regulating BMP signaling. Co-IP, ubiquitination assay, domain mapping, siRNA knockdown in zebrafish, siRNA injection in rat bone The EMBO journal High 21572392
2011 Smurf1 interacts with WFS1 (Wolfram syndrome protein) at the ER via the C-terminal luminal region of WFS1 (residues 667–700) and promotes its ubiquitination and proteasomal degradation; ER stress induces Smurf1 degradation and WFS1 up-regulation, suggesting feedback regulation. Co-IP, ubiquitination assay, domain mapping, siRNA, ER stress inducers The Journal of biological chemistry Medium 21454619
2011 Smurf1 interacts with and ubiquitinates KLF2 for proteasomal degradation specifically in lung cancer H1299 cells, requiring Smurf1's catalytic activity; this represses KLF2 transcriptional activity and alters expression of downstream targets (CD62L, Wee1). Co-IP, ubiquitination assay, catalytic mutant, reporter assay Biochemical and biophysical research communications Medium 21382345
2011 PKA-dependent phosphorylation of Smurf1 at Thr306 switches its substrate preference: Thr306-phosphorylated Smurf1 preferentially degrades RhoA over Par6; preventing this phosphorylation reduces axon formation in hippocampal neurons and impairs cortical neuron polarization in vivo. PKA phosphorylation assay, phospho-mimetic/resistant mutants, in vitro ubiquitination, cultured neuron axon formation assay, in utero electroporation Neuron High 21262463
2012 Ndfip1 enhances Smurf1 self-ubiquitination and its interaction with MAVS, promoting MAVS ubiquitination and degradation; Ndfip1 knockdown elevates MAVS levels and enhances RIG-I-dependent antiviral signaling. Co-IP, ubiquitination assay, siRNA knockdown, IFN-β reporter, IRF-3 phosphorylation assay Journal of immunology Medium 23087404
2012 Smurf1 interacts with STAT1 through its WW domains and the PY motif of STAT1, catalyzing K48-linked polyubiquitination and proteasomal degradation of STAT1 independently of STAT1 phosphorylation; Smurf1 overexpression attenuates IFN-γ signaling and antiviral response, while knockdown enhances them. Co-IP, domain mapping, ubiquitination assay (K48-linkage), siRNA, IFN-γ reporter, antiviral assay The Journal of biological chemistry High 22474288
2012 Deubiquitinase USP9X (FAM) interacts with Smurf1 via the second WW domain of Smurf1 and the C-terminus of USP9X, antagonizing Smurf1 autoubiquitination and protecting Smurf1 from self-degradation; USP9X depletion leads to Smurf1 down-regulation and impaired cell migration. Quantitative MS, Co-IP, domain mapping, ubiquitination assay, siRNA, migration assay The Journal of biological chemistry High 23184937
2013 Smurf1 ubiquitinates Axin via atypical K29-linked polyubiquitin chains (at K789 and K821) without inducing degradation; this modification disrupts Axin's interaction with LRP5/6 co-receptors and attenuates Wnt-stimulated LRP6 phosphorylation, thereby repressing Wnt/β-catenin signaling. Co-IP, in vitro ubiquitination assay, K29-linkage-specific analysis, site-directed mutagenesis, Wnt reporter, Smurf1-KO MEFs Molecular and cellular biology High 23959799
2013 Smurf1 induces non-degradative ubiquitination of TRAF4 at K190, which is required for proper localization of TRAF4 to tight junctions in confluent epithelial cells; this ubiquitination event is essential for TRAF4-mediated Rac1 activation and breast epithelial/cancer cell migration. Co-IP, ubiquitination assay with K190R mutant, localization by microscopy, Rac1 activation assay, migration assay The Journal of biological chemistry High 23760265
2013 Smurf1 directly interacts with and ubiquitinates TRIB2 (at a N-terminal domain, residues 1–5), a process requiring prior p70S6K-mediated phosphorylation of TRIB2 at Ser83; reduced p70S6K and Smurf1 in liver cancer leads to increased TRIB2 stability. Co-IP, ubiquitination assay, domain mapping, phospho-mutant analysis, half-life assay The Journal of biological chemistry Medium 24089522
2013 PKA-mediated phosphorylation of Smurf1 at Thr306 prevents JNK-triggered Nur77 degradation by enabling unconventional (non-degradative) ubiquitination of Nur77 by Smurf1, resulting in Nur77 accumulation and mitochondrial translocation to induce apoptosis in cisplatin-treated cells. PKA phosphorylation assay, ubiquitination assay, Nur77 stability assay, apoptosis readout, phospho-mimetic mutants Oncogene Medium 23584473
2014 Smurf1 is activated by neddylation: Smurf1 physically interacts with Nedd8 and Ubc12, forms a Nedd8-thioester intermediate, and auto-neddylates itself on multiple lysines via an active site at C426 in the HECT N-lobe; neddylation of Smurf1 enhances ubiquitin E2 recruitment and ubiquitin ligase activity. This regulatory mechanism is conserved in yeast Rsp5. In vitro neddylation assay, Nedd8-thioester intermediate detection, active-site mutagenesis (C426), yeast Rsp5 conservation test, ubiquitin E2 recruitment assay Nature communications High 24821572
2014 DNA damage (UV or MMS) activates ATR/Chk1, which phosphorylates Smurf1, enhancing Smurf1 self-degradation; this leads to RhoB accumulation and apoptosis. In the basal state, Smurf1 targets RhoB for degradation to control its abundance. Kinase assay, Smurf1 phospho-mutants, ubiquitination assay, apoptosis assay, Smurf1 overexpression/KD Nature communications High 25249323
2014 The C2 domain of Smurf1 mediates its interaction with Axin in a non-canonical manner (independent of WW-PY interaction); plasma membrane localization via the C2 domain is required for Axin ubiquitination. Smurf1-Axin interaction and K29-linked ubiquitination are attenuated in G2/M phase, correlating with increased Wnt responsiveness at that cell cycle stage. Co-IP, domain mapping, ubiquitination assay, cell cycle synchronization, Wnt reporter The Journal of biological chemistry Medium 24700460
2016 Smurf1 is required for selective autophagy of Mycobacterium tuberculosis (Mtb) in macrophages; Smurf1-/- macrophages fail to recruit polyubiquitin, NBR1, LC3, and LAMP1 to Mtb-associated structures. This function requires both the ubiquitin-ligase and C2 phospholipid-binding domains and involves K48-linked ubiquitination. Smurf1-/- mice show increased bacterial load and accelerated mortality. Smurf1-/- macrophages, domain mutant analysis, K48/K63-linkage ubiquitination assay, confocal microscopy for autophagy markers, in vivo mouse infection Cell host & microbe High 28017659
2016 AMPK-mediated phosphorylation of Smurf1 at Ser148 controls osteoblast differentiation: a S148A knock-in mutation (preventing AMPK phosphorylation) causes premature osteoblast differentiation phenotype equivalent to Smurf1-/-, high bone mass, and hyperinsulinemia/hypoglycemia through increased Runx2 accumulation and elevated insulin receptor levels (Smurf1 also targets the insulin receptor for degradation). Smurf1 S148 knock-in mouse, Runx2 protein levels, insulin receptor degradation assay, phosphorylation by AMPK Cell reports High 27052174
2016 Smurf1 deletion protects mice from pulmonary arterial hypertension; SMURF1 is identified as a key miR-140-5p target in PASMCs; SMURF1 knockdown alters BMP signaling in smooth muscle cells. Smurf1-/- mouse PAH model, miR-140-5p mimic delivery, SMURF1 siRNA, BMP signaling reporter The Journal of clinical investigation Medium 27214554
2017 Smurf1 interacts with Kindlin-2 and promotes its ubiquitination and degradation, thereby inhibiting αIIbβ3 and β1 integrin activation; Smurf1-KO MEFs show enhanced β1 integrin activation correlated with increased Kindlin-2 protein levels. Smurf1 selectively degrades Kindlin-2 but not Talin. Co-IP, ubiquitination assay, integrin activation assay, Smurf1-KO MEFs, colon cancer tissue correlation The Journal of cell biology High 28408404
2017 Smurf1 directly interacts with PIPKIγ via its C2 domain and ubiquitinates PIPKIγ at K255, targeting it for degradation; PKA-mediated phosphorylation of Smurf1 at Thr306 (or Smurf1-T306D phospho-mimetic) prevents PIPKIγ degradation, linking PKA-Smurf1 signaling to lung cancer cell growth. Co-IP, ubiquitination assay, domain mapping, phospho-mimetic mutants, in vitro kinase assay, tumor growth assay Oncogene Medium 28581524
2018 SMURF1 interacts with ERα via its HECT domain and inhibits K48-specific polyubiquitination of ERα, stabilizing ERα protein and promoting ERα-dependent transcription and breast cancer cell proliferation. Co-IP with domain mapping, ubiquitin immunoprecipitation (K48-specific), protein stability assay, ERα reporter, siRNA, xenograft Journal of experimental & clinical cancer research Medium 29433542
2018 Smurf1 mediates non-proteolytic K63-linked ubiquitination of PPARγ, suppressing its transcriptional activity; Smurf1-deficient mice develop spontaneous hepatic steatosis with up-regulated PPARγ target genes, and PPARγ antagonist treatment fully reverses lipid accumulation. Smurf1-KO mouse, K63-linkage-specific ubiquitination assay, PPARγ reporter, PPARγ antagonist rescue, high-fat diet experiment PLoS biology High 30566427
2018 SMURF1 is expressed at the primary cilium and at the outflow tract cushion mesenchyme during heart development; Smurf1-/- embryos show delayed outflow tract septation and reduced aortic smooth muscle layer thickness; Smurf1 promotes smooth muscle and cardiac fibroblast differentiation while negatively regulating cardiomyogenesis. Smurf1-/- mouse embryos, immunofluorescence localization to primary cilium, histomorphometry, differentiation marker analysis Scientific reports Medium 29934521
2018 CKIP-1 and Smurf1 are co-expressed at the chick neural plate border; CKIP-1 knockdown causes neural crest loss by suppressing BMP/pSmad1/5/8 signaling; Smurf1 overexpression mimics CKIP-1 loss (both reduce pSmad1/5/8); epistasis shows CKIP-1 rescues Smurf1-mediated neural crest loss by suppressing Smurf1-mediated Smad degradation. Morpholino knockdown, Smurf1 overexpression, BMP reporter, pSmad1/5/8 Western blot, epistasis (CKIP-1 rescue of Smurf1 OE) PLoS biology High 29949573
2019 SMURF1 ubiquitinates UVRAG at K517 and K559 via K29/K33-linked polyubiquitin chains, reducing UVRAG-RUBCN association and promoting autophagosome maturation; CSNK1A1-mediated phosphorylation of UVRAG at Ser522 blocks SMURF1 binding to UVRAG; deubiquitinase ZRANB1 removes SMURF1-catalyzed chains from UVRAG, restoring RUBCN binding. Co-IP, in vitro ubiquitination assay, site-directed mutagenesis, autophagosome maturation assay, kinase assay, deubiquitinase assay Autophagy High 30686098
2019 SMURF1 interacts with and ubiquitinates ARHGAP26, a negative regulator of RhoA (RhoA-GAP), promoting its degradation and thereby sustaining RhoA-GTP levels, which activates β-catenin signaling and promotes ovarian cancer cell invasion and migration. Co-IP, ubiquitination assay, ARHGAP26 overexpression/knockdown, RhoA-GTP pull-down, in vivo lung metastasis assay Experimental & molecular medicine Medium 31004081
2020 Smurf1 ubiquitylates and degrades PTEN, leading to PI3K/Akt/mTOR pathway activation; Smurf1-deficient glioblastoma cells have restored PTEN activity, reduced PI3K/Akt signaling, and are sensitized to rapamycin; combined Smurf1 knockdown plus rapamycin reduces tumor progression in an orthotopic GBM model. Co-IP, ubiquitination assay, PTEN activity assay, Smurf1 siRNA, in vivo orthotopic GBM model, rapamycin combination Oncogene Medium 32737433
2021 Smurf1 acts as a Nedd8 ligase (in addition to ubiquitin ligase) to catalyze neddylation of RRP9 (U3 snoRNP component) primarily at K221; RRP9 neddylation promotes pre-rRNA processing and ribosome biogenesis; unneddylated RRP9-K221R lacks tumor-promoting activity. NEDP1 removes Nedd8 from RRP9. In vivo and in vitro neddylation assay, site-directed mutagenesis (K221R), pre-rRNA processing assay, co-IP, functional tumor proliferation/migration assay The Journal of biological chemistry High 34662580
2021 SMURF1 ubiquitylates and degrades SHP-1 (a protein tyrosine phosphatase), activating STAT3 signaling; SMURF1 and SHP-1 protein levels are inversely correlated in endometriosis tissue, and SMURF1-mediated SHP-1 degradation promotes endometrial stromal cell proliferation and invasion. Co-IP, ubiquitination assay, Co-IP in patient tissues, siRNA/overexpression, STAT3 activation assay, invasion assay Annals of translational medicine Medium 33842583
2022 ERK phosphorylates Smurf1 at Thr223 upon TGFβ stimulation; this phosphorylation is a prerequisite for Smurf1-mediated RhoA polyubiquitination and degradation, cytoskeletal rearrangement, and EMT; blocking Thr223 phosphorylation inhibits TGFβ-induced EMT and dramatically reduces lung metastasis of murine breast cancer in vivo. Kinase assay, phospho-mutants, Co-IP, ubiquitination assay, EMT markers, in vivo lung metastasis Life science alliance High 35654587
2023 Smurf1 interacts with the TGR5 intracellular loop 2 (ICL2) region via its HECT domain and mediates K11/K48-linked polyubiquitination of TGR5 at K306, leading to proteasomal degradation of TGR5 under high glucose stimulation; genetic Smurf1 deficiency restores TGR5 and attenuates renal injury in diabetic mice. Co-IP, domain mapping, site-directed mutagenesis (K306R), K11/K48-linkage-specific ubiquitination assay, Smurf1-KO diabetic mouse model Cell reports High 37481723
2024 Smurf1 triggers PDK1 neddylation upon growth factor stimulation; poly-Nedd8 chains on PDK1 recruit methyltransferase SETDB1 to form a cytoplasmic complex (cCOMPASS: PDK1-Smurf1-SETDB1) that directs Akt membrane attachment and T308 phosphorylation; Smurf1 deficiency reduces CRC tumorigenesis; a Smurf1-specific degrader (SART-1) blocks PDK1-Akt signaling and suppresses KRAS-mutated CRC tumors. In vitro neddylation assay, Co-IP, Smurf1 genetic KO in CRC mouse model, Akt membrane recruitment assay, Smurf1 PROTAC degrader, PDK1 inhibitor combination Nature chemical biology High 39039255

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. The Journal of biological chemistry 707 11278251
2005 Ubiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation. Cell 311 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 265 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 244 12738770
2014 The covalent modifier Nedd8 is critical for the activation of Smurf1 ubiquitin ligase in tumorigenesis. Nature communications 186 24821572
2016 The Ubiquitin Ligase Smurf1 Functions in Selective Autophagy of Mycobacterium tuberculosis and Anti-tuberculous Host Defense. Cell host & microbe 182 28017659
2009 Talin phosphorylation by Cdk5 regulates Smurf1-mediated talin head ubiquitylation and cell migration. Nature cell biology 173 19363486
2003 Smurf1 inhibits osteoblast differentiation and bone formation in vitro and in vivo. The Journal of biological chemistry 170 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
2002 Smurf1 regulates the inhibitory activity of Smad7 by targeting Smad7 to the plasma membrane. The Journal of biological chemistry 152 12151385
2008 Targeting WW domains linker of HECT-type ubiquitin ligase Smurf1 for activation by CKIP-1. Nature cell biology 136 18641638
2016 MicroRNA-140-5p and SMURF1 regulate pulmonary arterial hypertension. The Journal of clinical investigation 128 27214554
2011 Phosphorylation of E3 ligase Smurf1 switches its substrate preference in support of axon development. Neuron 127 21262463
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 115 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 110 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 102 23184937
2011 Cdh1 regulates osteoblast function through an APC/C-independent modulation of Smurf1. Molecular cell 95 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 85 23007848
2013 Smurf1-mediated Lys29-linked nonproteolytic polyubiquitination of axin negatively regulates Wnt/β-catenin signaling. Molecular and cellular biology 83 23959799
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 82 20200942
2012 Smurf1 protein negatively regulates interferon-γ signaling through promoting STAT1 protein ubiquitination and degradation. The Journal of biological chemistry 76 22474288
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 73 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
2011 The E3 ligase Smurf1 regulates Wolfram syndrome protein stability at the endoplasmic reticulum. The Journal of biological chemistry 64 21454619
2017 MiR-503 Promotes Bone Formation in Distraction Osteogenesis through Suppressing Smurf1 Expression. Scientific reports 56 28341855
2016 Smurf1 Inhibits Osteoblast Differentiation, Bone Formation, and Glucose Homeostasis through Serine 148. Cell reports 56 27052174
2009 Ubiquitin ligase Smurf1 targets TRAF family proteins for ubiquitination and degradation. Molecular and cellular biochemistry 56 19937093
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
2018 Inhibition of osteoblastic Smurf1 promotes bone formation in mouse models of distinctive age-related osteoporosis. Nature communications 52 30143635
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 52 29248720
2011 TGFβ and BMP-2 regulate epicardial cell invasion via TGFβR3 activation of the Par6/Smurf1/RhoA pathway. Cellular signalling 52 22033038
2005 Ubiquitination of RhoA by Smurf1 promotes neurite outgrowth. FEBS letters 52 15710384
2022 The mechanosensitive lncRNA Neat1 promotes osteoblast function through paraspeckle-dependent Smurf1 mRNA retention. Bone research 51 35210394
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 51 33425934
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.) 51 20558834
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
2011 SMURF1 amplification promotes invasiveness in pancreatic cancer. PloS one 46 21887346
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 44 28408404
2011 Pivotal role of the C2 domain of the Smurf1 ubiquitin ligase in substrate selection. The Journal of biological chemistry 44 21402695
2018 USF2 inhibits the transcriptional activity of Smurf1 and Smurf2 to promote breast cancer tumorigenesis. Cellular signalling 42 30244169
2013 Impaired phosphorylation and ubiquitination by p70 S6 kinase (p70S6K) and Smad ubiquitination regulatory factor 1 (Smurf1) promote tribbles homolog 2 (TRIB2) stability and carcinogenic property in liver cancer. The Journal of biological chemistry 42 24089522
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
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 40 18208356
2017 The Role of Smurf1 in Neuronal Necroptosis after Lipopolysaccharide-Induced Neuroinflammation. Cellular and molecular neurobiology 39 28940129
2017 Smurf1 regulates lung cancer cell growth and migration through interaction with and ubiquitination of PIPKIγ. Oncogene 38 28581524
2013 CKIP-1 acts as a colonic tumor suppressor by repressing oncogenic Smurf1 synthesis and promoting Smurf1 autodegradation. Oncogene 38 23995790
2011 Binding of RhoA by the C2 domain of E3 ligase Smurf1 is essential for Smurf1-regulated RhoA ubiquitination and cell protrusive activity. FEBS letters 38 21708152
2014 SMURF1 silencing diminishes a CD44-high cancer stem cell-like population in head and neck squamous cell carcinoma. Molecular cancer 37 25471937
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
2019 miR-4319 inhibited the development of thyroid cancer by modulating FUS-stabilized SMURF1. Journal of cellular biochemistry 35 31148243
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
2020 TGFβ1 Suppressed Matrix Mineralization of Osteoblasts Differentiation by Regulating SMURF1-C/EBPβ-DKK1 Axis. International journal of molecular sciences 34 33371439
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
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 31 28847510
2018 Smurf1 regulates macrophage proliferation, apoptosis and migration via JNK and p38 MAPK signaling pathways. Molecular immunology 30 29550577
2013 PKA/Smurf1 signaling-mediated stabilization of Nur77 is required for anticancer drug cisplatin-induced apoptosis. Oncogene 30 23584473
2016 Smurf1 regulation of DAB2IP controls cell proliferation and migration. Oncotarget 29 27036023
2018 The E3 ubiquitin ligase SMURF1 regulates cell-fate specification and outflow tract septation during mammalian heart development. Scientific reports 27 29934521
2020 SMURF1, a promoter of tumor cell progression? Cancer gene therapy 26 33204002
2019 SND1 facilitates the invasion and migration of cervical cancer cells by Smurf1-mediated degradation of FOXA2. Experimental cell research 26 31891682
2024 Targeting Smurf1 to block PDK1-Akt signaling in KRAS-mutated colorectal cancer. Nature chemical biology 25 39039255
2023 Enhanced liquidity of p62 droplets mediated by Smurf1 links Nrf2 activation and autophagy. Cell & bioscience 25 36810259
2021 Neddylation modification of the U3 snoRNA-binding protein RRP9 by Smurf1 promotes tumorigenesis. The Journal of biological chemistry 25 34662580
2018 Role of SMURF1 ubiquitin ligase in BMP receptor trafficking and signaling. Cellular signalling 25 30395943
2018 Non-proteolytic ubiquitin modification of PPARγ by Smurf1 protects the liver from steatosis. PLoS biology 25 30566427
2010 Identification of substrates of SMURF1 ubiquitin ligase activity utilizing protein microarrays. Assay and drug development technologies 25 20804422
2016 Transcription factor Six2 mediates the protection of GDNF on 6-OHDA lesioned dopaminergic neurons by regulating Smurf1 expression. Cell death & disease 24 27148690
2015 F-box protein Fbxo3 targets Smurf1 ubiquitin ligase for ubiquitination and degradation. Biochemical and biophysical research communications 24 25721664
2022 ERK-Smurf1-RhoA signaling is critical for TGFβ-drived EMT and tumor metastasis. Life science alliance 23 35654587
2017 Uev1A facilitates osteosarcoma differentiation by promoting Smurf1-mediated Smad1 ubiquitination and degradation. Cell death & disease 23 28771228
2014 Smurf1 plays a role in EGF inhibition of BMP2-induced osteogenic differentiation. Experimental cell research 23 24631292
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
2006 Smurf1 regulates neural patterning and folding in Xenopus embryos by antagonizing the BMP/Smad1 pathway. Developmental biology 22 16973150
2020 MiR-195 enhances cardiomyogenic differentiation of the proepicardium/septum transversum by Smurf1 and Foxp1 modulation. Scientific reports 21 32518241
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
2021 SMURF1-mediated ubiquitylation of SHP-1 promotes cell proliferation and invasion of endometrial stromal cells in endometriosis. Annals of translational medicine 20 33842583
2023 The degradation of TGR5 mediated by Smurf1 contributes to diabetic nephropathy. Cell reports 19 37481723
2018 IRAK2 counterbalances oncogenic Smurf1 in colon cancer cells by dictating ER stress. Cellular signalling 19 29753111

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